Gems from "The Type 1 Diabetes Sourcebook"

Leave it to Anne Peters MD to be co-editor of this amazing resource for medical providers who treat patients with Type 1 diabetes (Type 1 Diabetes Sourcebook, 2013. Anne Peters, MD, and Lori Laffel, MD, MPH, Editors. JDRF and American Diabetes Association). The book is written for the Type 1 medical community, but I think it has a lot of good information for the patient with Type 1 diabetes. Unlike so many books on Type 1 diabetes that only focus on kids, this one addresses both children AND adults with Type 1 diabetes, and notes that adults represent 85% of the Type 1 population. I also appreciate the level of compassion shown in the book towards those with T1D—in particular, I am so unused to compassion expressed towards people with adult-onset Type 1 diabetes, but this excellent book has it in abundance. Here are direct-quote gems that I found in The Type 1 Diabetes Sourcebook (keeping in mind that my usual focus is adult-onset Type 1 diabetes):

• There is no authoritative source for the incidence of T1D in adults in the U.S. population. However, it is important to note that T1D is not a childhood disease and may be diagnosed into adulthood with an additional peak in the sixth and seventh decades of life [emphasis mine]. Page 1.
• Recent data are needed regarding the incidence of T1D in adults. Notably, nearly 85% of people living with Type 1 diabetes are adults. Page 8.
• Adults developing T1D may follow a less precipitous course with few or no symptoms and an elevated glucose level identified incidentally on routine blood work. These individuals may be treated (unsuccessfully) with oral agents before it is determined that they are actually patients with evolving T1D who need treatment with insulin [emphasis mine]. Page 3.
• Initial Treatment for Adults: Adult patients can vary greatly at presentation, from a more acute picture, with DKA and marked hyperglycemia, to a more gradual course such as is often seen in LADA. For those presenting acutely as well as those presenting more indolently, starting insulin is the mainstay of therapy [emphasis mine]. Page 79.
• We want [medical] providers to know that patients with T1D are not the same as patients with T2D; thus, we describe the specific approaches for patents with T1D across the life span. Page 73.
• The pathophysiology of the two diseases [T1D and T2D] differ on a basic pathophysiologic level such that T1D is marked by insulinopenia while T2D is characterized by obesity, hyperinsulinemia, insulin resistance, and relative insulinopenia. Page 104.
• Regarding diagnostic criteria (ADA, WHO): As the ADA/WHO diagnostic criteria are heavily influenced by the overwhelming burden of T2D worldwide, clinicians must recall that these criteria are not T1D specific and do not always provide optimal sensitivity for the diagnosis of T1D. ADA and WHO criteria are used to broadly diagnose diabetes, however, a combination of immunologic, genetic, and phenotypic features must be used to differentiate among the different forms of diabetes. Page 4 and 5.
• We consider all patients with evidence of autoimmunity to have T1D. Page 5.
• Given the tremendous burden T2D places on the U.S. health care system, it is not surprising that patients, health care providers, and researchers often use the nonspecific term diabetes when referring to T2D. However, the practice of referring to T2D as simply diabetes cultivates numerous dangerous misconceptions regarding the etiology, pathophysiology, and treatment of other subtypes of diabetes [emphasis mine]. Page 6.
• Despite the historical focus on children when discussing the epidemiology of T1D, it is critical to consider that adults make up 25-50% of newly diagnosed patients and represent the overwhelming majority of patients living with T1D. Importantly, adults with LADA may represent an additional 10% of those adults incorrectly diagnosed with T2D. As these patients are far more likely to progress rapidly to requiring insulin therapy, clinicians treating adults must be aware of the need to screen for LADA, particularly in their patients with relatively low BMI. [Elsewhere in the book, on page 24, the authors state that 60% of new-onset T1D is seen in adults, and that is confirmed by the most recently available data from the CDC.]
• [In persons with LADA], failure to control glucose [with non-insulin therapies for T2D] should rapidly lead to insulin therapy rather than allowing months to years of experimenting with non-insulin approaches [emphasis mine]. Page 24.
• It is often unappreciated that many individuals with T1D will have significant amounts of C-peptide, representing residual beta cell function. The standard teaching that T1D is defined as complete absence of beta cells is inaccurate and is a disservice to both patients and providers. Among 411 participants in the Joslin Medalists study (those with T1D greater than or equal to 50 years), 67.4% still had detectable C-peptide. Pages 26 and 27.
• For those with early T1D, expert opinion (i.e., not data driven) recommends either low doses of basal insulin to prevent DKA or prandial insulin to prevent postprandial hyperglycemia. Page 27.
• Preservation trials focus on halting further pancreatic beta cell destruction after T1D diagnosis. At the time of diagnosis, it has been estimated that 15-40% of beta cell function remains. This remnant can serve one well while it lasts, as evidenced by better overall glycemic control during this remission or honeymoon phase, with lower A1Cs, less glycemic variability, and less hypoglycemia risk. Page 42.

Originally published at Tudiabetes.org

Wrong Assumptions Lead to False Conclusions: Diabetes Rising by Dan Hurley

Dan Hurley, author of the 2011 book Diabetes Rising and diagnosed with Type 1 diabetes at age 18, makes several substantive errors in his book that lessen the credibility of his “investigative journalism,” in my opinion.  Mr. Hurley (1) incorrectly assumes that ancient descriptions of diabetes were of Type 2 diabetes because those descriptions involved adults not children,  2) promotes Dr. Terence Wilkin’s assertion that Type 1 diabetes and Type 2 diabetes are on a continuum of diabetes, and (3) says that a once rare disease has become a pandemic.  All three are not true.  Although the book is a fascinating read, these fundamental errors lessen the impact of his narrative—incorrect assumptions lead to false conclusions.

New-Onset Type 1 Diabetes Occurs in Both Adults and Children

Mr. Hurley opens Chapter 1 of Diabetes Rising with descriptions of diabetes from ancient times.  Early descriptions of diabetes, including Aretaeus of Cappadocia, clearly described what is now called Type 1 diabetes (polyuria, polydipsia, rapid weight loss and swift death).  But Mr. Hurley concludes that these descriptions must be of Type 2 diabetes, for the reason that the descriptions were of "adults, not children, whose symptoms typically came on slowly (as they often do in type 2), not quickly (as they almost always do in type 1.")  And yet new-onset Type 1 diabetes is diagnosed throughout the lifespan and is not a childhood disease, so it is no surprise that Aretaeus of Cappadocia described adults.  Mr. Hurley says, “Nearly all the early description of diabetes are plainly of Type 2, involving adults, not children…” and Mr. Hurley wonders why these early physicians did not note that the patients were obese (“yet they never noticed that the leading risk factor for the disease is obesity” and “Rather than suspecting them of being dull-witted when it comes to something so obvious [obesity].”)  But the early physicians were not dull-witted; they were describing the disease now called Type 1 diabetes, and they did not mention weight other than to remark on the thinness of patients, because the patients were not obese—obesity is not a risk factor for Type 1 diabetes.

In Principles of Diabetes Mellitus, 2^nd Edition (Leonid Poretsky, MD, Editor), the authors in Chapter 1 write:  “A medical condition producing excessive thirst, continuous urination, and severe weight loss has interested medical authors for over three millennia.  Unfortunately, until the early part of the twentieth century the prognosis for a patient with this condition was no better than it was over 3000 years ago.  Since the ancient physicians described almost exclusively cases of what is today known as Type 1 diabetes mellitus [emphasis mine], the outcome was invariably fatal.”  The early descriptions of diabetes, including the vivid description by Aretaeus the Cappadocian, clearly are of what we know today as Type 1 diabetes.

Regarding age of onset, let’s look at the facts:  actress and Chair of JDRF International Mary Tyler Moore was diagnosed with Type 1 diabetes at age 33.  Dr. Kenneth Moritsugu, former acting U.S. Surgeon General, was diagnosed with Type 1 diabetes at age 49.  Dr. Anne Peters, a prominent endocrinologist, editor of The Type 1 Diabetes Sourcebook, and co-author of the American Diabetes Association’s (ADA’s) 2014 position statement “Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association” says that the oldest patient she has diagnosed with Type 1 diabetes was 92 years old.  Dr. Irl Hirsch, a prominent diabetes researcher who has Type 1 diabetes himself, says the oldest patient that he has diagnosed with Type 1 diabetes was 86 years old.  The U.S. Centers for Disease Control and Prevention (CDC) information on the prevalence and incidence of Type 1 diabetes indicates that the majority of new onset Type 1 diabetes is seen in adults[1].  Dr. Elliott Joslin, in 1934, noted that the incidence of diabetes in lean individuals was relatively constant in each decade of life, but that diabetes in the obese was related to older age. A book published in 1958 (“How to Live with Diabetes” by Henry Dolger, M.D. and Bernard Seeman) that states that “[Type 1] diabetes is almost three times more frequent among young adults than among youngsters.”  Mr. Hurley devotes considerable ink to the landmark Diabetes Control and Complications Trial (DCCT), whose study subjects all have Type 1 diabetes, but neglects to mention that many of the 1,441 study subjects were adults when they were diagnosed with Type 1 diabetes.  On page 20, Mr. Hurley neglects to mention that both emaciated diabetic children but also emaciated diabetic adults under Frederick M. Allen’s care were saved by the discovery of insulin in 1922 ("virtually overnight emaciated diabetic children who had been clinging to life by the thread....were able to put on pounds and regain their strength" with no mention of the adults who were also saved).  It is an outdated myth that Type 1 diabetes is “juvenile” diabetes and is a childhood disease.

Type 1 Diabetes and Type 2 Diabetes are Different Diseases

In much of Diabetes Rising, Mr. Hurley does make the distinction between the two diseases, Type 1 diabetes and Type 2 diabetes, but Chapter 5 is devoted to Dr. Terence J. Wilkin's "accelerator hypothesis," and Dr. Wilkin's "audacious idea that type 1 and type 2 are really one disease, distinguishable only in degrees."  However, early physicians understood that “diabetes mellitus” represented several diseases.  In the 1970s, Type 1 diabetes was determined to be an autoimmune disease, the result of an immune-mediated destruction of the beta cells, and distinguished from Type 2 diabetes which is not autoimmune[2].  As stated in The Type 1 Diabetes Sourcebook (ADA/JDRF 2013), the pathophysiology of the two diseases [T1D and T2D] differ on a basic pathophysiologic level such that Type 1 diabetes is marked by insulinopenia while Type 2 diabetes is characterized by obesity, hyperinsulinemia, insulin resistance, and relative insulinopenia.  Sue Kirkman MD, professor of medicine at University of North Carolina and one of four authors of the ADA position statement “Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association” says “Type 1 diabetes is a completely different disease than Type 2 and needs to be treated as such.”  Type 1 diabetes is an autoimmune disease, and the presence of autoantibodies confirms Type 1 diabetes.  Yet to justify that Type 1 and 2 are really the same disease, Dr. Wilkin cited studies that found that 20 to 29 percent of people with Type 2 diabetes had at least one of the autoantibodies normally associated with type 1 diabetes (Diabetes Rising, p. 98)[3].  What Dr. Wilkin fails to recognize, and Mr. Hurley did not correct, is that the presence of autoantibodies in a person diagnosed with “Type 2” diabetes means that the person has been misdiagnosed and has Type 1 diabetes, since autoantibodies are never present in Type 2 diabetes by definition—autoimmune diabetes is Type 1 diabetes.  The problem of misdiagnosis (adults with new-onset Type 1 diabetes who are misdiagnosed as having Type 2 diabetes, based on age not etiology) is enormous, but only recently being recognized (see for example the Wall Street Journal’s “Wrong Call:  The Trouble Diagnosing Diabetes,” August 2012).   In the Wall Street Journal article, Robin Goland, co-director of the Naomi Berrie Diabetes Center at Columbia University Medical Center in New York, states “Most of my [adult Type 1 patients] have been misdiagnosed as having Type 2 diabetes.”  Michael J. Haller MD, in Type 1 Diabetes Sourcebook (ADA/JDRF, 2013), says “Importantly, adults with LADA [latent autoimmune diabetes in adults or slowly progressive Type 1 diabetes] may represent an additional 10% of those adults incorrectly diagnosed with Type 2 diabetes.”  It shows a lack of scientific rigor to fail to differentiate between Type 1 and Type 2 diabetes; they are different diseases, not different forms of one disease, and the two diseases have different genetics, causes, treatments, and potential cures.

Diabetes as a Rare Disease

It is sensationalistic and sells books to say that a once rare disease, diabetes, is now an epidemic or pandemic, but it is false.  As I substantiated previously, early descriptions of the once rare disease were of Type 1 diabetes, and Type 1 and Type 2 diabetes are altogether different diseases.  Although rates of Type 1 diabetes have increased (especially if the misdiagnosed are correctly included in the statistics for T1D), it is Type 2 diabetes that is the epidemic.  The incidence of Type 2 diabetes has dramatically increased in recent decades, much more rapidly than Type 1 diabetes.  The once rare disease, Type 1 diabetes, has not become the pandemic of Type 2 diabetes.

The problem of misdiagnosis is enormous and tragic—it typically results in the withholding of life-saving care for patients with a treatable disease.  Books such as Diabetes Rising contribute to the misinformation surrounding Type 1 diabetes; by promoting these factual errors, Mr. Hurley reduces the impact of his work, which is unfortunate because much of Diabetes Rising is a rarely seen, in-depth look at the realities of Type 1 diabetes and Type 2 diabetes.

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[1] The U.S. Centers for Disease Control and Prevention’s (CDC’s) most current information on the prevalence and incidence of Type 1 diabetes comes from Diabetes in America, Chapter 3, “Prevalence and Incidence of Insulin-Dependent Diabetes” (Diabetes in America, Second Edition, 1995).  That source states that children (<20 years of age) account for 13,171 cases and adults (>20 years of age) account for 16,542 cases, for a total of 29,713 new cases of Type 1 diabetes per year, 56% seen in adults.  Furthermore, that source states that there is an unknown number of adults identified as having Type 2 diabetes who actually have slowly progressive Type 1 diabetes. The number of people with slowly progressive Type 1 diabetes is quite large, consistently about 10% of “Type 2” diabetes based on autoantibody testing (for example, the first study that demonstrated that about 10% of people with “Type 2” diabetes are autoantibody positive was published in The Lancet in 1977.  In the UKPDS, about 10% of people diagnosed with “Type 2” diabetes were autoantibody positive and had been misdiagnosed).  Clinicians use autoantibody tests to distinguish between Type 1 autoimmune diabetes and non-autoimmune diabetes (Type 2 diabetes, monogenic diabetes, etc.).

[2] The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA/WHO), as published in American Diabetes Association medical journals, says, "Although the specific etiologies of [Type 2] diabetes are not known, autoimmune destruction of beta-cells does not occur."  The Expert Committee’s definition of Type 1 diabetes clearly encompasses all autoimmune diabetes, regardless of age (“Type 1 diabetes results from a cellular-mediated autoimmune destruction of the beta-cells of the pancreas. In Type 1 diabetes, the rate of beta-cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults)).” 

[3] Autoantibodies include glutamic acid decarboxylase autoantibodies (GAD), islet cell cytoplasmic autoantibodies (ICA), insulinoma-associated 2 autoantibodies (IA-2), insulin autoantibodies (IAA), and zinc transporter 8 autoantibodies (ZnT8).  IAA can only be tested if exogenous insulin has not yet been used.  Other autoantibodies may exist but have not yet been identified.

Latent Autoimmune Diabetes Myths: The Patient-Centered Perspective

Latent Autoimmune Diabetes in Adults (LADA) is a term coined by Tuomi et al in 1993[1] to describe slow-onset Type 1 diabetes.  The NIDDK (U.S. National Institute of Diabetes and Digestive and Kidney Diseases) says LADA is “a condition in which Type 1 diabetes develops in adults.”  The WHO (World Health Organization) includes LADA in the category of Type 1 diabetes.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus[2] does not recognize the term LADA; rather, the Expert Committee includes LADA in the definition of Type 1 autoimmune diabetes:  “Type 1 diabetes results from a cellular-mediated autoimmune destruction of the beta-cells of the pancreas. In Type 1 diabetes, the rate of beta-cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults).”  Most childhood-onset Type 1 diabetes is rapid onset, whereas in adulthood both rapid-onset and slowly progressive Type 1 diabetes occur.  Initially the term LADA was useful to shine light on this group of people with slowly progressive T1D, because people with LADA are so often misdiagnosed as having Type 2 diabetes (an altogether different disease), and because LADA is two to three times more common than classic onset Type 1 diabetes.[3]  However, numerous researchers now favor elimination of the term, instead moving to “autoimmune diabetes” to describe immune-mediated diabetes at all ages.

Type 1 diabetes, including LADA, is characterized by autoimmune destruction of the beta cells of the pancreas.  Markers for the immune-mediated destruction of the beta cells include autoantibody markers glutamic acid decarboxylase autoantibodies (GAD), islet cell cytoplasmic autoantibodies (ICA), insulinoma-associated 2 autoantibodies (IA-2), insulin autoantibodies (IAA), and zinc transporter 8 autoantibodies (ZnT8).  Other autoantibodies may exist but have not yet been discovered.  T1D/LADA is associated with HLA DR3/4 genes.

Despite the fact that LADA is Type 1 diabetes, many in the medical profession/diabetes community irrationally try to say that LADA is somehow not Type 1 diabetes.  Here are the myths versus the facts:

Myth:  Because LADA has a slower onset than classic Type 1 diabetes in children, it is a different disease.

Fact:  Onset of Type 1 diabetes in babies is much more rapid than Type 1 diabetes in teenagers, but no one in the medical community is saying that those teenagers should be kicked out of the Type 1 Club.  It is the disease process, not rate of onset, that defines Type 1 diabetes.

Myth:  People with LADA have genes associated with Type 2 diabetes.

Fact:  A significant percentage of the total population has genes associated with Type 2 diabetes, including people with rapid-onset Type 1 diabetes and LADA.  T1D/LADA is associated with HLA DR3/4 genes.

Myth:  People with LADA have only one autoantibody, GAD65, whereas people with rapid-onset Type 1 diabetes have more autoantibodies.

Fact:  In a recent study of people with adult-onset Type 1 diabetes, 24% had two or more autoantibodies[4], and many children with rapid-onset Type 1 are only GAD positive.  What counts is the presence of ANY autoantibody:  if the person (either child or adult) has been diagnosed with diabetes (fasting blood glucose greater than 125 mg/dl) and the person is positive for any one autoantibody, the person has Type 1 autoimmune diabetes.

Myth:  People with LADA have insulin resistance, so they don’t have Type 1 diabetes.

Fact:  Many people diagnosed with Type 1 diabetes as children develop insulin resistance later in life.  No one kicks them out of the Type 1 Club because they later develop IR.  Recent large-scale studies indicate that people with both classic onset Type 1 diabetes and those with LADA have a similar prevalence of metabolic syndrome to a non-diabetic control group but metabolic syndrome was significantly higher in those with Type 2 diabetes.[5]

Myth:  LADA is a “hybrid” form of Type 1 AND Type 2 diabetes.

Fact:  Some people with LADA have insulin resistance, so they have Type 1 diabetes and insulin resistance.  Most LADAs do not have insulin resistance.  No medical researcher is saying that Type 1 kids who develop insulin resistance have “hybrid” diabetes.  No, the kid has Type 1 diabetes, and so does the adult.

Myth:  LADA is a different disease than classic Type 1 diabetes because people with LADA still have some endogenous insulin production.

Fact:  Among 411 participants in the Joslin Medalists study (those with duration of T1D greater than or equal to 50 years), 67.4% still had detectable C-peptide, meaning they still have some endogenous insulin production.  As stated in The Type 1 Diabetes Sourcebook, “It is often unappreciated that many individuals with T1D will have significant amounts of C-peptide, representing residual beta cell function. The standard teaching that T1D is defined as complete absence of beta cells is inaccurate and is a disservice to both patients and providers.”[6]

Myth:  LADA is a different disease because people with LADA don’t initially require insulin for survival, and people with classic onset Type 1 diabetes immediately require insulin.

Fact:  Prior to 1922, Frederick Allen kept children with rapid-onset Type 1 diabetes alive for 5 years or more with a very low carbohydrate/very low calorie diet.  But now that we have excellent insulins, there is no reason to deny ANY person with Type 1 diabetes/LADA the insulin that they need.

Myth:  LADA describes adult phenotypic Type 2 diabetes.

Fact:  “Phenotype” is the composite of an organism's observable characteristics or traits, and an observant doctor or medical researcher would realize that the traits of a person with LADA are markedly different than the traits of a person with Type 2 diabetes, including the presence of autoantibodies in LADA, which are not present in Type 2 diabetes.  People with LADA are adult phenotypic Type 1 diabetes, based on characteristics and traits.

  

Myth:  People with LADA can be treated initially with drugs for Type 2 diabetes.

Fact:  In the 1970s in the United States, children with Type 1 diabetes were sometimes initially treated with sulfonylureas for up to 1 year, to keep the child off of insulin injections for as long as possible.  That practice was abandoned, as it should be for people with adult-onset Type 1 diabetes.  Type 1 diabetes, at whatever age it is diagnosed, should be treated with insulin, not with drugs for Type 2 diabetes, an altogether different disease.  Type 2 drugs are not likely to be effective, in any case.  As stated in the Type 1 Diabetes Sourcebook, “starting insulin is the mainstay of therapy” for adults who present acutely with Type 1 diabetes as well as those presenting more indolently.  Regarding adult-onset Type 1 diabetes, the T1D Sourcebook also says, “for those with early T1D, expert opinion recommends either low doses of basal insulin to prevent DKA [diabetic ketoacidosis] or prandial insulin to prevent postprandial hyperglycemia.”  Clinical studies have conclusively demonstrated that early and intensive exogenous insulin therapy controls glucose levels, prevents further destruction of residual beta cells, reduces the possibility of diabetic complications, and prevents death from diabetic ketoacidosis (DKA).

Myth:  A person who is overweight or obese has Type 2 diabetes, and cannot have Type 1 diabetes/LADA.

Fact:  Some children are overweight or obese at diagnosis of Type 1 diabetes.  By the same token some adults are overweight or obese at diagnosis of T1D/LADA.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus states, “Although patients are rarely obese when they present with [Type 1 diabetes], the presence of obesity is not incompatible with the diagnosis.”  A Swedish study emphasizes that diagnosis based on “etiology is superior to clinical judgment.”[7]

In researching these myths, one thing that I found to be extremely sad and disturbing is the lack of compassion shown towards those with adult-onset Type 1 diabetes.  Most of the research in journals never considers what might be best for the human being with Type 1 diabetes.  (Often researchers will say there is no reason to initiate insulin therapy at diagnosis, that treatment with drugs for Type 2 diabetes is the first-line treatment, and that autoantibody testing is too expensive to be used for anything more than research studies.  I would remind those researchers First Do No Harm.)  A misdiagnosed adult recently said to me, “I hope that more medical professionals realize how misdiagnosing adults with type 2 diabetes instead of type 1 can be dangerous and carries a very significant mental and physical toll on the newly diagnosed diabetic.” The exception to this lack of compassion is the excellent book by Dr. Anne Peters and Dr. Lori Laffel, Type 1 Diabetes Sourcebook (2013, American Diabetes Association/JDRF), which demonstrates compassion in abundance.  Kudos to those editors.

First published as a TuDiabetes.org blog

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[1] Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes. 1993;42:359–62.

[2] Diabetes Care January 2012 vol. 35 no. Supplement 1 S64-S71.

[3] Type 1 Diabetes in Adults: Principles and Practice (Informa Healthcare, 2008), page 27.

[4] “Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype” (DIABETES CARE, VOLUME 36, APRIL 2013).

[5] Metabolic Syndrome and Autoimmune Diabetes: Action LADA 3.  Mohammed I. Hawa, Charles Thivolet, Didac Mauricio, Irene Alemanno, Elisa Cipponeri, David Collier, Steven Hunter, Raffaella Buzzetti, Alberto de Leiva, Paolo Pozzilli, Richard David G. Leslie, on behalf of the Action LADA Group.  Diabetes Care. 2009 January; 32(1): 160–164.

[6] Type 1 Diabetes Sourcebook, 2013. Anne Peters, MD, and Lori Laffel, MD, MPH, Editors. JDRF and American Diabetes Association.  Page 26.

[7] “Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 years) in the Diabetes Incidence Study in Sweden (DISS).” Springer-Verlag, 2003.

Acute-Onset Type 1 Diabetes in Adults: Overlooked and Ignored

Rapid onset Type 1 diabetes in childhood, previously called "juvenile diabetes," gets the most visibility; it affects about 15,000 children per year in the United States[1].  Slowly progressive Type 1 diabetes (aka LADA (latent autoimmune diabetes in adults)) is now garnering much more attention, mostly in medical research journals but now more frequently in mainstream publications.  By my calculations, slowly progressive Type 1 diabetes (LADA) represents the vast majority of all new cases of Type 1 diabetes annually; new-onset LADA affects about 145,000 adults per year, or about 10% of new cases of “Type 2” diabetes in the United States[2].  But what about the adults with acute-onset Type 1 diabetes, who actually outnumber those children with new-onset Type 1 diabetes[3]?  Tragically we are overlooked, ignored, and still usually misdiagnosed as Type 2 diabetes based on age not etiology.

I experienced acute-onset Type 1 diabetes at age 35, but was misdiagnosed by the hospital’s on-call endocrinologist as having Type 2 diabetes, based on age not phenotype.  Fortunately, I only remained misdiagnosed for one week.  I recently polled members of the diabetes social media site TuDiabetes.org, and here are some select stories and commentaries about acute-onset Type 1 diabetes, and what the adult with T1D wishes medical practitioners understood:

• At age 30, soon after she retired as professional ballet dancer, Kris was misdiagnosed as having Type 2 diabetes and told by her doctor to lose weight (at 5’6” tall, Kris weighed less than 100 pounds) and exercise more. Her doctor scolded her when the “lifestyle changes” that he ordered did nothing for her, because in her doctor’s mind the problem was that Kris was not following his directives.  Kris went into diabetic ketoacidosis, lapsed into a coma, and thankfully was found by friends and rushed to the emergency room.  Initially in the emergency room the doctors accused her of not following her treatment protocol thereby bringing DKA upon herself, until they called in an endocrinologist who realized she had been misdiagnosed and given incorrect treatment.  In the ER, the endocrinologist correctly diagnosed Kris as having Type 1 diabetes.
• Michael, a competitive bicyclist, was misdiagnosed as having Type 2 diabetes at age 42.  Others advised Michael to get autoantibody testing, which his doctor initially refused to perform.  Finally, when his doctor reluctantly ordered the autoantibody tests and the tests came back positive, his doctor sent him a letter via snail mail saying he “might” have Type 1 diabetes.  Michael was denied insulin for 12 months.
• Marybeth was hospitalized in DKA at the age of 60, but incorrectly diagnosed as having Type 2 diabetes strictly based on age, not etiology.  Marybeth was fit, active, normal weight, and displayed extreme sensitivity to insulin in the ER.  Six months prior to hospitalization, Marybeth’s fasting blood glucose was 74 mg/dl at a health screening, indicating that her diabetes onset was rapid. Marybeth says, “If I had followed my hospital discharge instructions I would probably be dead” and “Clinicians need to be brought up to date on the incidence of Type 1 diabetes in adults. They need to look at the whole picture. Emergency room doctors especially need to use their brains not just a blindly follow a Standard Operating Procedure (SOP).”
• Jen, misdiagnosed at age 22, says, “I hope that more medical professionals realize how misdiagnosing adults with type 2 diabetes instead of type 1 can be dangerous and carries a very significant mental and physical toll on the newly diagnosed diabetic.”

In polling members of TuDiabetes, I was struck by the degree to which the medical community downplays the seriousness of adult-onset Type 1 diabetes.  Children with new-onset Type 1 diabetes are given due respect; yet all too often adults are told they don’t even deserve correct diagnosis and treatment.  This perception is slowly changing—The Type 1 Diabetes Sourcebook (ADA/JDRF, 2013) recognizes the seriousness of adult-onset Type 1 diabetes and the need for correct diagnosis and appropriate treatment.  Dr. Steven Edelman, founder of Taking Control of Your Diabetes (TCOYD), advocates correct diagnosis and treatment, and at the medical education lectures that Dr. Edelman gives around the United States he encourages medical practitioners to look out for LADA patients and order autoantibody testing.  Slowly, the tide is turning.

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[1] SEARCH for Diabetes in Youth, research sponsor U.S. Centers for Disease Control and Prevention (CDC).

[2] This is an estimated number based on 37 years of autoantibody testing that indicates that approximately 10% of people diagnosed with “Type 2” diabetes are autoantibody positive and by definition have Type 1 autoimmune diabetes.  Michael J. Haller MD, in Type 1 Diabetes Sourcebook (ADA/JDRF, 2013), says “Importantly, adults with LADA may represent an additional 10% of those adults incorrectly diagnosed with Type 2 diabetes.”  The first study that demonstrated that about 10% of people with “Type 2” diabetes are autoantibody positive was published in The Lancet in 1977, now 37 years ago (Irvine WJ, Gray RS, McCallum CJ, Duncan LJP: Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. Lancet1 :1025–1027,1977).  In the United Kingdom Prospective Diabetes Study (UKPDS), about 10% of people diagnosed with “Type 2” diabetes were autoantibody positive and had been misdiagnosed.

[3] The U.S. Centers for Disease Control and Prevention’s (CDC’s) most current information on the prevalence and incidence of Type 1 diabetes comes from Diabetes in America, Chapter 3, “Prevalence and Incidence of Insulin-Dependent Diabetes” (Diabetes in America, Second Edition, 1995).  Although people who use that reference as a source of incidence statistics state that there are about 30,000 new cases of Type 1 diabetes each year and that half of those cases are children; in fact, that source states that children (<20 years of age) account for 13,171 cases and adults (>20 years of age) account for 16,542 cases, for a total of 29,713 new cases of Type 1 diabetes per year, 56% seen in adults.  Thus, new cases of acute-onset T1D in adults exceed new cases of acute-onset T1D in children.  Additionally, that source states that there is an unknown number of adults identified as having Type 2 diabetes who have slowly progressive Type 1 diabetes.

Bill of Rights for People with Adult-Onset Type 1 Diabetes Or “A Manifesto for the Misdiagnosed”

There are many names for adult-onset Type 1 diabetes, including latent autoimmune diabetes in adults (LADA)[1], Type 1.5 diabetes, and slowly progressive Type 1 diabetes[2].  Although the majority of new-onset Type 1 diabetes always has been seen in adults[3], the myth that Type 1 diabetes is a childhood disease often means adults with Type 1 are misdiagnosed as having Type 2 diabetes and/or given substandard treatment.  Here is my manifesto:

·         Correct diagnosis:  If an adult is diagnosed with diabetes and does not appear to fit a more typical profile for Type 2 diabetes (i.e., the adult is not overweight, does not have abdominal obesity, is not insulin resistant, does not have a family history of Type 2 diabetes, and does not have metabolic syndrome), the person should be tested to see if he/she has Type 1 autoimmune diabetes.  The gold-standard test for Type 1 diabetes is autoantibody testing (glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulin autoantibodies, insulinoma-associated (IA-2) autoantibodies, and zinc transporter autoantibodies (ZnT8)), and the c-peptide test is also useful but not definitive.  If the person is autoantibody positive, he/she has Type 1 diabetes.

·         Insulin treatment:  Intensive insulin therapy should begin as quickly as possible in the newly diagnosed adult with Type 1 diabetes.  The correct treatment for Type 1 diabetes, at whatever age it is diagnosed, is exogenous insulin as early as possible, to control glucose levels, prevent further destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from diabetic ketoacidosis (DKA). [4]

·         Appropriate education:  An adult who is newly diagnosed with Type 1 diabetes should receive Type 1 diabetes-specific education, not Type 2 diabetes education.  Type 2 diabetes is a different disease with different genetics, causes, treatments, and potential cures.

·         Autoimmune gestational diabetes:  Many if not most of medical professionals are not aware that gestational diabetes may be a precursor to Type 1 diabetes, not just Type 2 diabetes.  The stress of pregnancy is "the straw that broke the camel's back" for many women who develop Type 1 diabetes during pregnancy (autoimmune gestational diabetes).  Again, antibody testing can be used to distinguish autoimmune gestational diabetes, and women with autoimmune gestational diabetes should begin intensive insulin therapy immediately.[5]

·         Inclusion in appropriate statistics:  People with adult-onset Type 1 diabetes should be included in statistics addressing prevalence and incidence of Type 1 diabetes.  At the present time, most adult-onset Type 1s are included in figures for the numbers of Type 2 diabetics.   In information distributed to laypeople, the U.S. Centers for Disease Control and Prevention (CDC) and the American Diabetes Association (ADA) consistently say that Type 2 diabetes represents 90-95% of cases of diabetes in America and that Type 1 diabetes represents 5-10% of all cases of diabetes. However, this is incorrect according to ADA’s own peer-reviewed scientific journals. That 90-95% Type 2 statistic includes people with LADA, and according to the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (as published in ADA journals), "Although the specific etiologies of [Type 2] diabetes are not known, autoimmune destruction of beta-cells does not occur."  The National Institutes of Health (NIH (NIDDK)) defines LADA as a condition in which Type 1 diabetes develops in adults.  Furthermore, the Expert Committee’s definition of Type 1 diabetes by the clearly encompasses all autoimmune diabetes, regardless of age, which includes LADA (“Type 1 diabetes results from a cellular-mediated autoimmune destruction of the beta-cells of the pancreas. In Type 1 diabetes, the rate of beta-cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults).”)  According to Irl Hirsch M.D., member of the Expert Committee, “The term latent autoimmune diabetes of adults (LADA) as originally described represents perhaps as many as 10­ to 20% of adult-onset patients with diabetes.”  Doing the math, Type 1 diabetes represents about 20% of all people with diabetes.

·         Inclusion in clinical trials:  People with adult-onset Type 1 diabetes should not be excluded from clinical trials for Type 1 diabetes strictly because of age.  For example, Type 1 Diabetes TrialNet excludes many Type 1 diabetics and their families based on age at diagnosis.  Type 1 autoimmune diabetes is diagnosed based on epidemiology, not age; therefore, TrialNet is not truly representative of the full scope of Type 1 diabetes.  Former acting U.S. Surgeon General Dr. Kenneth Moritsugu, who was diagnosed with Type 1 diabetes at age 49, would be excluded from Type 1 Diabetes TrialNet.

All people with Type 1 diabetes deserve to be correctly diagnosed and be given disease-appropriate treatment, yet for many people with adult-onset Type 1 diabetes that is not happening today.

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[1] More recently, diabetes researchers have discouraged the use of the term latent autoimmune diabetes in adults, because LADA is not a latent disease.  One group has proposed the term ADASP (autoimmune diabetes in adults with slowly progressive beta cell failure), but this term seems cumbersome.

[2] Some adult-onset Type 1 diabetes is acute onset, similar to what most children experience.  I had acute-onset Type 1 diabetes.

[3] The U.S. Centers for Disease Control and Prevention’s (CDC’s) most current information on the prevalence and incidence of Type 1 diabetes comes from Diabetes in America, Chapter 3, “Prevalence and Incidence of Insulin-Dependent Diabetes” (Diabetes in America, Second Edition, 1995).  Although people who use that reference as a source of incidence statistics state that there are about 30,000 new cases of Type 1 diabetes each year and that half of those cases are children; in fact, that source states that children (<20 years of age) account for 13,171 cases and adults (>20 years of age) account for 16,542 cases, for a total of 29,713 new cases of Type 1 diabetes per year, 56% seen in adults.  Furthermore, that source states that there is an “unknown number of adults identified as Type 2 diabetes who have slowly progressive Type 1 diabetes.”  In summary, of those new onset Type 1 diabetics who are correctly diagnosed, 56% are adults, and an unknown number of new-onset Type 1 diabetics have been misdiagnosed as having Type 2 diabetes and thus the majority of new onset Type 1 diabetes is seen in adults.

[4] In the Diabetes Control and Complications Trial (DCCT), all subjects with adult-onset Type 1 diabetes had some residual beta cell function (Bernard Zinman MD, DCCT).  Those who were assigned to the intensive insulin therapy group were slower to lose residual beta cell function than the conventional therapy group (risk reduction 57%).  Clearly, early intensive insulin therapy has enormous benefit.  As demonstrated in the DCCT, “intensive therapy for Type 1 diabetes helps sustain endogenous insulin secretion, which, in turn, is associated with better metabolic control and lower risk for hyperglycemia and chronic complications.”  LADA researchers in Japan (Kobayashi et al, 2002) have conclusively demonstrated that better preservation of beta cell function occurs with exogenous insulin compared to sulfonylureas, and that sulfonylureas hasten beta cell destruction.  In other words, doctors may inappropriately use Type 2 therapies in new-onset Type 1 diabetes, but all scientific studies indicate that the correct therapy is intensive insulin therapy.

[5] In Europe, the literature on gestational diabetes mentions autoimmune gestational diabetes, but in North America the layperson literature doesn't mention it. However, the existence of autoimmune gestational diabetes is widely reported in North American scientific literature (for example, a July 2007 "Diabetes Care" article and also an April 2003 "Diabetes Care" article on GDM). The July 2007 issue of "Diabetes Care" indicated that autoimmune gestational diabetes (new onset Type 1 diabetes) accounts for about 10% of all Caucasian women diagnosed with gestational diabetes (Diabetes Care July 2007 vol. 30 no. Supplement 2 S105-S111 ). It says “A small minority (≤10% in most studies) of women with GDM have circulating antibodies to pancreatic islets (anti-islet cell antibodies) or to β-cell antigens such as GAD (anti-GAD antibodies)” and then notes, “They appear to have evolving type 1 diabetes that comes to clinical attention through routine glucose screening during pregnancy. Whether pregnancy can actually initiate or accelerate islet-directed autoimmunity is unknown.”

Melitta’s Top Ten Tips for the Newly Diagnosed Person with Adult-Onset Type 1 Diabetes

In no particular order:

1)    Despite what you may be told by medical professionals and what you might read, you (as a person with adult-onset Type 1 diabetes) are not “rare” or some “minority.”  Adults represent the majority of new-onset Type 1 diabetes--recent epidemiological data have shown that more than half of all new cases of type 1 diabetes occur in adults (Footnote 1). It is a widespread myth and falsehood that Type 1 diabetes is a childhood disease.

2)    Learn all you can, but at a pace that does not overwhelm you.  Good sources of learning are Think Like a Pancreas by Gary Scheiner (although he does perpetuate some myths about adult-onset Type 1 diabetes/LADA, but the rest is excellent) and my new favorite Bright Spots and Landmines:  The Diabetes Guide I Wish Someone Had Handed Me by Adam Brown of DiaTribe.  Sugar Surfing by Stephen Ponder and Kevin McMahon is diabetes management gold.  Using Insulin and Pumping Insulin by John Walsh are older but excellent, and the Type 1 University (https://type1university.com/) is a great source for learning specific skills. Taking Control of Your Diabetes (TCOYD) sponsors an annual ONE Conference that is outstanding. JDRF has a T1D Care Kit for newly diagnosed adults that is very good (JDRF Adult Toolkit). Be wary of the Internet—there is lots of good, but there is lots of very bad.

3)    Get a correct diagnosis:  many if not most people with adult-onset Type 1 diabetes are misdiagnosed as having Type 2 diabetes.  It is important to get a correct diagnosis to get the correct treatment (exogenous insulin); being treated as if you have Type 2 diabetes may be extremely harmful.  Get the full suite of antibody testing (Glutamic Acid Decarboxylase Autoantibodies (GADA), Islet Cell Cytoplasmic Autoantibodies (ICA), Insulinoma-Associated-2 Autoantibodies (IA-2A), Insulin Autoantibodies (IAA), and zinc transporter 8 autoantibodies (ZnT8) (Footnote 2).  Don’t just get GADA, because a small but significant percentage of people are GADA-negative but positive for one of the other autoantibodies.  Autoantibody testing is the gold standard test for Type 1 autoimmune diabetes:  if you are antibody positive, you have Type 1 autoimmune diabetes. [Note that although the vast majority of people with Type 1 diabetes are autoantibody positive, those with idiopathic Type 1 diabetes are not.  This could be because there are yet undiscovered autoantibodies, or some other reason.]  The c-peptide test, which shows how much insulin you are producing (virtually all children and adults with new-onset Type 1 diabetes are still producing some endogenous insulin), is useful, but does not provide a definitive diagnosis.

4)    Begin intensive insulin therapy as soon as you are able.  The correct treatment for Type 1 diabetes, at whatever age it is diagnosed, is exogenous insulin as early as possible, to control glucose levels, slow the destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from diabetic ketoacidosis (DKA).  Many adults can prolong the “honeymoon” period (the time when some remnant beta cells are still producing insulin) with intensive insulin therapy (including using an insulin pump).  If a pump seems like too much or insurance will not cover one, MDI (multiple daily injections) is good.  Early insulin use and prolonging the honeymoon period will make it easier to control your diabetes and greatly reduce the risk of diabetic complications, thus making your life better.  Some people with very slow onset Type 1 diabetes may not need insulin immediately (Footnote 3).  But insulin should not be avoided due to fear.

5)    Allow yourself time and space to grieve.  The diagnosis of Type 1 diabetes is devastating for most people.  As an adult, you may wonder what you did wrong to precipitate Type 1 diabetes (the answer is nothing, it is an autoimmune disease).  Grieving often takes a lot of time, more time than we care to admit or allow, so it is important to give feelings of anger, denial, and depression their due.  Get the support you need from family, friends, online (TuDiabetes.org forums; some excellent Facebook groups), and a therapist (preferably one with knowledge of chronic illness) if you want.  JDRF has groups for adults. Do things that bring you joy and well-being:  exercise, yoga, meditation, gardening, petting dogs/cats, music, etc.  Remember you have been given a second chance at life; make it count.  Balancing Diabetes:  Conversations About Finding Happiness and Living Well by Kerri Sparling has great tips for living better.  Diabetes Sucks and You Can Handle It: Your Guide to Managing the Emotional Challenges of T1D by Mark Heyman, a psychologist and person with T1D, is excellent; Dr. Mark also has a podcast. An older book that I think is excellent is Psyching Out Diabetes: A Positive Approach to Your Negative Emotions (Rubin, Biermann, and Toohey.  1997). The Behavioral Diabetes Institute (http://behavioraldiabetesinstitute.org/) is also superb in this area.

6)    Consider the wise advice of people at the Behavioral Diabetes Institute:  maintain the best blood sugar control you can, avoid lows (hypoglycemia) especially severe lows, and live your life.  Don’t think that a cure for Type 1 diabetes is coming anytime soon.  If you are a Type A personality, be especially wary of being harsh on yourself for some number on a meter/CGM and be wary of trying to achieve some “perfect” A1c.

7)    Test, test, test.  Lots of blood glucose testing means better control.  If you can, get a continuous glucose monitor (CGM), which in the case of Dexcom gives a blood glucose reading every 5 minutes, and also lets you know what direction your blood glucose is trending.  Don’t allow embarrassment to prevent you from taking proper care of yourself (meaning, if you need to test or inject in public, do it.)  Eat to your meter (use your blood glucose meter/CGM to test your blood sugar after meals and eliminate from your diet the foods that spike your blood sugar).  Follow the rule of small numbers (from Dr. Bernstein:  big inputs make big mistakes; small inputs make small mistakes—in other words, lower carb means lower doses of insulin means smaller “mistakes”). 

8)    Get organized; get your security blanket in order.  For me, security comes in the form of backup—I carry my diabetes kit with me at all times.  My diabetes kit includes insulin vial and needles, meter and test strips, glucose tabs, and backup supplies for my insulin pump.  I wear a Medic Alert (www.medicalert.org) bracelet that says I have Type 1 diabetes, an insulin pump, and that I have autoimmune hypothyroidism (Hashimoto’s disease).

9)    Use your healthcare team.  Find good people who you can work with and who work with you as an individual.  Your team might include an endocrinologist, diabetes care and education specialist (DCES), nutritionist, and psychologist. Be your own best advocate in the healthcare system.

10) Get tested for Hashimoto’s Disease and celiac disease, two autoimmune diseases that are commonly seen in people with Type 1 autoimmune diabetes.

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Footnote 1:  R David Leslie et al. Adult-Onset Type 1 Diabetes: Current Understanding and Challenges. Diabetes Care 2021;44:2449-2456..

Footnote 2:  IAA test does not distinguish between autoantibodies that target the endogenous insulin and antibodies produced against exogenous insulin. Therefore, this test is not valid for someone who has already been treated with injections of insulin. For example, someone who was thought to have Type 2 diabetes and who was treated with insulin injections cannot then have this test done to determine if they have Type 1 diabetes.
Footnote 3:  Some people whose Type 1 diabetes is slowly progressive and is caught early can go without exogenous insulin for a time (however, insulin should not be avoided due to fear, either on the part of the person with T1D or his/her/their doctor).  Dr. Anne Peters, the acclaimed endocrinologist and co-editor of The Type 1 Diabetes Sourcebook, is positive for four autoantibodies, although she does not yet have symptomatic Type 1 diabetes.  Dr. Peters is using liquid metformin and Ozempic (a GLP-1 receptor agonist) to try to preserve her beta cells.  Also, a recent study (IK Hals et al, Diabetes Obes Metab 2019;1-9) found that exogenous insulin and the DPP-4 inhibitor sitagliptin worked equally well to preserve beta cell function in people with slowly progressive Type 1 diabetes (note that the older insulin, NPH, was given once a day in the insulin arm of the study, meaning 24 hour coverage with exogenous insulin did not occur).  For those that are not on exogenous insulin, it is a good idea to have some on hand in case one's blood sugar rises rapidly due to illness, etc.