How Does Type 1 Diabetes Develop? T1D Etiopathogenesis

Often, I hear people say that a certain event caused them to develop Type 1 diabetes, such as an accident, a stressful time in their lives, or pregnancy, but in fact the actual disease process begins far before such an event, perhaps years before. Another misconception that I hear often is that the autoantibodies destroy the pancreatic beta cells, but it is actually killer T cells. Type 1 diabetes is characterized by immune-mediated destruction of pancreatic beta cells in genetically predisposed individuals, which results in severe insulin deficiency and the need for exogenous insulin to sustain life.  In Type 1 autoimmune diabetes, the healthy insulin-producing beta cells of the pancreas are destroyed by T-cells of the immune system, which mistake the beta cells as “foreign” and attack them. Here are the sequential steps in the development of Type 1 diabetes:

Step 1: Genetic Predisposition

People genetically predisposed to Type 1 diabetes have either HLA-DR3-DQ2 or HLA-DR4-DQ8 haplotypes, or both [Footnote 1].  Some HLA epitopes protect against the development of Type 1 diabetes; the presence of resistance HLA epitopes has been correlated with a later age of onset (adult-onset Type 1 diabetes) [Footnote 2].

Step 2: Immune Activation/Environmental Trigger

It is still not known what triggers the immune-mediated destruction of the beta cells, but it is related to environmental factors that are still poorly defined [Footnote 3]. Type 1 diabetes was first described in detail in about 100 C.E. by Aretaeus of Cappadocia [Footnote 4], so whatever the environmental factors are, they have been present for thousands of years.

Step 3: Immune Response/Development of Autoantibodies

During the immune activation and immune response involved in Type 1 diabetes, the immune system mistakenly attacks beta cells in the pancreas and destroys them over time, ultimately resulting in insulin deficiency. This process leads to the production of islet-specific autoantibodies (GAD, ICA, IA-2, IAA, and ZnT8); the autoantibodies are not pathogenic, but they represent biomarkers of the pathogenesis [Footnote 5].  Or put another way, diabetes autoantibodies are proteins that mark insulin-producing beta cells for destruction, but the autoantibodies are not believed to be directly pathological.

Step 4: Triggering Event

The triggering event is any event that stresses the body, such as illness, accident, or even pregnancy.  The stressful event means that the body requires additional insulin for proper functioning, but the ongoing destruction of the beta cells means that insufficient insulin is secreted in response to the stressor. This event is a tipping point or “the straw that broke the camel’s back,” but it is not causal.

Step 5: Development of Overt Type 1 Diabetes

Type 1 Diabetes TrialNet has identified three stages of progression in Type 1 diabetes. In stage 1, a person tests positive for autoantibodies, blood sugar levels remain normal, and the individual is asymptomatic. In Stage 2, individuals are autoantibody positive, there is a loss of beta cells, blood sugar levels are abnormal, and typically there are no symptoms. In stage 3, Type 1 diabetes symptoms are present due to significant beta cell loss. Common symptoms include increased thirst and urination, extreme hunger, unexplained rapid weight loss, blurred vision, and extreme fatigue. Exogenous insulin is necessary to sustain life. Note that in adults with slowly progressive Type 1 diabetes, symptoms may be far milder, which often leads to adults with new-onset T1D being misdiagnosed as having Type 2 diabetes (an altogether different disease).

Footnote 1: The majority of studies of HLA association with Type 1 diabetes have used Caucasian subjects.

Footnote 2:  Multiple HLA Epitopes Contribute to Type 1 Diabetes Susceptibility.  CL Roark et al. Diabetes 2014 Jan; 63(1): 323-331.

Footnote 3:  American Diabetes Association (ADA) Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care 2020; 43 (Suppl 1): S14-S31.

Footnote 4: Aretaeus of Cappadocia, “Diabetes is a remarkable affliction, not very frequent among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts… The nature of the disease, then, is chronic, and it takes a long period to form; but the patient is short-lived, if the constitution of the disease be completely established; for the melting is rapid, the death speedy. Moreover, life is disgusting and painful; thirst, unquenchable; excessive drinking, which, however, is disproportionate to the large quantity of urine, for more urine is passed; and one cannot stop them either from drinking or making water. Or if for a time they abstain from drinking, their mouth becomes parched and their body dry; the viscera seems as if scorched up; they are affected with nausea, restlessness, and a burning thirst; and at no distant term they expire. They thirst, as if scorched up with fire … But if it increases still more, the heat is small indeed, but pungent, and seated in the intestines; the abdomen is shriveled, the veins protuberant, and there is general emaciation, when the quantity of urine and the thirst have already increased; and when, at the same time, the sensation appears at the extremity of the member, the patients immediately make water. Hence, the disease appears to me to have got the name diabetes as if from the Greek word διαβήτης (which signifies a siphon), because the fluid does not remain in the body, but uses the man’s body as a ladder, whereby to leave it. They survive not for long, for they pass urine with pain, and the emaciation is dreadful; nor does any great portion of the drink get into the system, and many parts of the flesh pass out along with the urine”. From Adams F (ed), 1856.The extant works of Aretaeus the Cappadocian. The Sydenham Society, London.

Footnote 5: If a single islet autoantibody or multiple islet autoantibodies are detected in a person diagnosed with diabetes (fasting blood sugar greater than 125 mg/dl), the diagnosis of Type 1 autoimmune diabetes is confirmed.

ADA Acknowledges “Misdiagnosis is Common,” CDC Indirectly Acknowledges Undercounting of Cases of Type 1 Diabetes

Twenty-five years ago, I began my advocacy on behalf of people with adult-onset Type 1 diabetes, shortly after I was misdiagnosed at age 35.  At that time, it was the position of the American Diabetes Association (ADA) and Centers for Disease Control and Prevention (CDC) that Type 1 diabetes was a childhood disease, and the organizations did not acknowledge misdiagnosis as a problem.  Back then, doctors would become enraged when I used the term “misdiagnosis.”  Finally, more than a quarter century later, the ADA has stated that misdiagnosis is common (since Type 1 and Type 2 are altogether different diseases, yes, it is misdiagnosis).  Additionally, CDC’s National Diabetes Statistics Report 2020 indirectly references the problem of undercounting of Type 1’s and misdiagnosis, by categorizing people who self-report in surveys that they went on insulin within one year of diagnosis as having Type 1 diabetes.

These changes from leading organizations are very positive—we have come a long way, but we are not there yet.  Misdiagnosis and undercounting continue to hamper people’s access to the appropriate care and treatment of Type 1 diabetes.  But this change of position by the ADA and CDC is a fantastic step which will hopefully pave the way for people with adult-onset Type 1 diabetes to receive a correct diagnosis, appropriate care, and overall better outcomes.

In this blog I provide excerpts from ADA’s Standards of Medical Care in Diabetes 2020 and CDC’s National Diabetes Statistics Report 2020.

Here are some pearls from ADA Standards of Medical Care in Diabetes 2020 [all emphasis is mine]:

“Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical presentation and disease progression may vary considerably. Classification is important for determining therapy, but some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms of type 2 diabetes occurring only in adults and type 1 diabetes only in children are no longer accurate, as both diseases occur in both age-groups. Children with type 1 diabetes typically present with the hallmark symptoms of polyuria/polydipsia, and approximately one-third present with diabetic ketoacidosis (DKA). The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may experience temporary remission from the need for insulin.

It is important for the provider to realize that classification of diabetes type is not always straightforward at presentation and that misdiagnosis is common (e.g., adults with type 1 diabetes misdiagnosed as having type 2 diabetes; individuals with maturity-onset diabetes of the young [MODY] misdiagnosed as having type 1 diabetes, etc.). Although difficulties in distinguishing diabetes type may occur in all age-groups at onset, the diagnosis becomes more obvious over time.

Characterization of the underlying pathophysiology is more developed in type 1 diabetes than in type 2 diabetes. It is now clear from studies of first-degree relatives of patients with type 1 diabetes that the persistent presence of two or more islet autoantibodies is an almost certain predictor of clinical hyperglycemia and diabetes. The rate of progression is dependent on the age at first detection of autoantibody, number of autoantibodies, autoantibody specificity, and autoantibody titer.

There is debate as to whether slowly progressive autoimmune diabetes with an adult onset should be termed latent autoimmune diabetes in adults (LADA) or whether the clinical priority is awareness that slow autoimmune β-cell destruction means there may be long duration of marginal insulin secretory capacity. For the purpose of this classification, all forms of diabetes mediated by autoimmune β-cell destruction are included under the rubric of type 1 diabetes.

Immune-mediated diabetes, previously called “insulin-dependent diabetes” or “juvenile-onset diabetes,” accounts for 5–10% [Note 1] of diabetes and is due to cellular-mediated autoimmune destruction of the pancreatic β-cells. Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD (GAD65), insulin, the tyrosine phosphatases IA-2 and IA-2β, and zinc transporter 8 (ZnT8). The disease has strong HLA associations, with linkage to the DQA and DQB genes. These HLA-DR/DQ alleles can be either predisposing or protective.

The rate of β-cell destruction [in Type 1 diabetes] is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults). Children and adolescents may present with DKA as the first manifestation of the disease. Others have modest fasting hyperglycemia that can rapidly change to severe hyperglycemia and/or DKA with infection or other stress. Adults may retain sufficient β-cell function to prevent DKA for many years; such individuals may have remission or decreased insulin needs for months or years and eventually become dependent on insulin for survival and are at risk for DKA

Although patients are not typically obese when they present with type 1 diabetes, obesity is increasingly common in the general population and there is evidence that it may also be a risk factor for type 1 diabetes. As such, obesity should not preclude the diagnosis.”

Melitta’s Note 1:  Type 1 diabetes that is correctly diagnosed accounts for 5-10% of all cases of diabetes.  However, as the Standards of Care point out, misdiagnosis is common, and in fact ~10% of people diagnosed with “Type 2” diabetes are autoantibody positive, have been misdiagnosed, and in fact have Type 1 diabetes.  Therefore, Type 1 diabetes represents more than 5-10% of all cases of diabetes.  See the CDC National Diabetes Statistics Report for additional information.

CDC National Diabetes Statistics Report 2020

“Most estimates of diabetes in this report do not differentiate between type 1 and type 2 diabetes. However, as type 2 diabetes accounts for 90% to 95% of all diabetes cases, the data presented here are more likely to be characteristic of type 2 diabetes, except as noted.

Prevalence of diagnosed diabetes:

• 210,000 children and adolescents younger than age 20 years—or 25 per 10,000 US youths— had diagnosed diabetes. This includes 187,000 with type 1 diabetes.
• 1.4 million adults aged 20 years or older—or 5.2% of all US adults with diagnosed diabetes—reported both having type 1 diabetes and using insulin.
• 2.9 million adults aged 20 years or older—or 10.9% of all US adults with diagnosed diabetes—started using insulin within a year of their diagnosis

APPENDIX B of the National Diabetes Statistics Report: Detailed Methods and Data Sources: Validated methods to distinguish between types of diabetes in surveys are not available. The percentage of adults aged 20 years or older with diagnosed diabetes who self-reported type 1 diabetes plus current insulin use and the percentage of adults aged 20 years or older with diagnosed diabetes who started using insulin within a year of their diagnosis were estimated from 2017 NHIS data. To estimate the number of adults aged 20 years or older with type 1 diabetes, these percentages were then applied to the derived number of adults aged 20 years or older with diagnosed diabetes.”

Reflections on Living with Type 1 Diabetes for 25 Years

April 13, 1995:  When I was 35 years old, my health declined rapidly, and I was hospitalized in diabetic ketoacidosis (DKA). Before 1922 and the discovery of insulin, I would have died then and there.  I was devastated, and I cried through the entire night at the hospital.  I knew several people who had Type 1 diabetes, and their lives were really difficult, and I feared that for myself. In that moment, I never imagined I would live another 25 years with this disease, free of complications, much less learn to thrive with it.  I was also incredibly active and loved traveling the world, and I thought that I would be constrained.  When I was diagnosed, my mother was about to leave for a trip to Bhutan, in the Himalayas, where she would be completely unreachable.  Mom told me she wouldn’t go, which was quite unlike her, but I insisted she go on her trip to Bhutan and she did (years later, I would travel to Bhutan as well). My father called me every day while Mom was gone, to check up on me.  Even though family and friends did their best to comfort me and be there for me, it was the scariest moment of my life.  

Fast forward 25 years, and I am happy to say I have a great life.  There have been bumps and challenges along the way but through each of those obstacles, I have become stronger and more resolved to live my best life and help others along the way.  I am using technology to manage my diabetes that I never thought I would see in my lifetime.  I wear an insulin pump (Tandem tSlim with ControlIQ) that is linked with a continuous glucose monitor (CGM) in what is called automated insulin delivery. It is nothing short of a miracle. I continue to travel the world, not without some challenges along the way, but I do it (except not now, since we are sheltering in place due to the coronavirus). My last big trip was 2+ weeks trekking in the Peruvian Andes, where our highest elevation was a 14,550 ft pass.

I have learned a lot along the way and my journey is far from over. I am very grateful that I am a scientist, because managing Type 1 diabetes is a big science experiment. I have successfully advocated for the recognition that Type 1 diabetes is not a childhood disease—I still have a long way to go and much to accomplish, but I have seen progress.  I started a blog to help people who are diagnosed with Type 1 diabetes as adults, most of whom are tragically misdiagnosed as having Type 2 diabetes, an altogether different disease, due to the persistence of the myth that Type 1 diabetes is a childhood disease. I met many others with Type 1 diabetes, and discovered I am not alone.  I belong to a club of very determined people who are living every day with purpose and zest. The Type 1 friends I have met along the way are such a gift—thank you all. I have learned to slow down—when I was first diagnosed, my older sister told me that I was too driven and needed to slow down, and she was right.  Six months before I was diagnosed I began practicing yoga, and yoga and meditation have helped me to unwind.

After 25 years of living with Type 1 diabetes, my approach is now grounded in experience.  I take the best care of myself as possible, embrace and lean on my support network along the way, do a lot of exercise/yoga/meditation (my magic pills), help others especially the newly diagnosed (kindness and compassion are necessities), and live my life to the fullest (which includes a lot of traveling).  It hasn’t always been easy, and it was a really rocky start at diagnosis, but I have done my best for these 25 years and I have an amazing life for which I am grateful every day.

Letter to the President of the American Academy of Family Physicians (AAFP) on misdiagnosis (T1D misdiagnosed as T2D)

Many of the adults who are misdiagnosed as having Type 2 diabetes, when they actually have Type 1 diabetes, are misdiagnosed by family physicians. Unfortunately, there is little awareness in the medical community of adult-onset Type 1 diabetes, and the American Academy of Family Physicians guidelines Diabetes Mellitus: Screening and Diagnosis (2016) present incorrect information about adult-onset Type 1 diabetes. Below is a letter that I wrote in 2018 to the President of the American Academy of Family Physicians and the authors of Diabetes Mellitus: Screening and Diagnosis.

Dear Dr. Munger:

The vision of the American Academy of Family Physicians (AAFP) is to transform health care to achieve optimal health for everyone.  The mission of AAFP is to improve the health of patients, families, and communities by serving the needs of members with professionalism and creativity.

Those are admirable vision and mission statements, but they are not being applied to people with adult-onset Type 1 diabetes, who are too often incorrectly diagnosed by Family Physicians who are provided incorrect information and inadequate guidelines by AAFP.

First, let’s look at what respected endocrinologists say about the epidemic of adult-onset Type 1 diabetes being misdiagnosed as Type 2 diabetes, which is an altogether different disease:

• Dr. Irl Hirsch, a professor of medicine at the University of Washington and former chairman of the Professional Practice Committee of the American Diabetes Association, has described the misdiagnosis of adult-onset Type 1 diabetes as an “epidemic.” He blames a lack of awareness and insufficient medical training about diabetes as the reason why so many patients fall through the gaps. The problem is particularly frustrating because there is a simple blood test that can check for antibodies associated with Type 1 diabetes, which could easily be used in diagnosing patients.  Dr. Hirsch quickly orders autoantibody tests when he is unsure of the correct diagnosis (Footnote 1). In Dr. Hirsch’s busy clinic, they see approximately one new person per week who is misdiagnosed (diagnosed as Type 2 when the person actually has Type 1).
• Dr. Robin Goland, co-director of the Naomi Berrie Diabetes Center at Columbia University Medical Center in New York, says "Most of my [adult-onset Type 1 patients] have been misdiagnosed as having Type 2.  Once the right diagnosis is made the patient feels much, much better, but they are distrustful of doctors and who could blame them (Footnote 2)?"
• Dr. Regina Castro, an endocrinologist at the Mayo Clinic, estimates that anywhere between 10 to 30 percent of adults diagnosed with Type 2 diabetes each year may in fact have Type 1 diabetes.  Exactly how many adults with Type 1 diabetes are misdiagnosed each year in the United States is hard to track—in  2015, the year for which data is most recently available, 1.5 million adults were diagnosed with diabetes, which is how, even taking the conservative end of Castro’s estimate, one gets to the possibility that tens of thousands if not hundreds of thousands go misdiagnosed each year.  “It is under-recognized and more prevalent than we think,” says Dr. Castro (Footnote 3).
• Dr. Steve Edelman, the founder and director of Taking Control of Your Diabetes (TCOYD), had this to say about misdiagnosis, “Latent autoimmune diabetes in adults (LADA) is the most misdiagnosed area in diabetes. We [Steve Edelman, Jeremy Pettus, Tricia Santos] are primarily adult endocrinologists and see tons of folks who are misdiagnosed.” (Personal communication)

Probably the most notable person to be misdiagnosed is UK Prime Minister Theresa May.  At the age of 56, Prime Minister May was misdiagnosed as having Type 2 diabetes; about 6 months after the initial misdiagnosis, she was correctly diagnosed as having Type 1 diabetes (Footnote 4).

Next, let’s look at what the AAFP guidelines Diabetes Mellitus: Screening and Diagnosis (2016) say about Type 1 diabetes, and then see how the guidelines stand up against the evidence-based facts.

AAFP 2016: Type 1 diabetes is caused by autoimmune destruction of the islet cells of the pancreas, and onset is typically in childhood.

Fact:  Type 1 diabetes is not a childhood disease.  The incidence of autoimmune diabetes is about equal in almost all age groups; adult-onset Type 1 diabetes is more common than childhood-onset Type 1 diabetes (Footnotes 5 & 6).

AAFP 2016:  Type 1 diabetes patients typically present with an acute onset of symptoms.

Fact:  Onset of Type 1 diabetes can be rapid or slowly progressive, with those with slowly progressive Type 1 diabetes far outnumbering those with rapid onset.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus’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)”).  From The Type 1 Diabetes Sourcebook (ADA/JDRF 2013), “Adult [Type 1] 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 latent autoimmune diabetes in adults (LADA).” 

AAFP 2016:  Some patients with latent autoimmune diabetes in the adult or Type 2 diabetes may have certain autoantibodies present making these tests less specific.

Fact:  By definition, those with LADA are autoantibody positive, and by definition of ADA and WHO, LADA is Type 1 diabetes.  Also by definition of ADA and WHO, "Although the specific etiologies of [Type 2] diabetes are not known, autoimmune destruction of beta-cells does not occur."   In other words, if a person has been diagnosed with Type 2 diabetes but is autoantibody positive, the person has been misdiagnosed and in fact has Type 1a diabetes.  This makes autoantibody testing more specific, not less.

AAFP 2016:  Despite these concerns [AAFP:  that autoantibodies are not specific to Type 1 diabetes], the American Association of Clinical Endocrinologists recommend routine confirmation of Type 1 diabetes using autoantibody testing.

Fact:  As established above, AAFP’s arguments that autoantibody tests are “less specific” are not true.  In fact, autoantibody testing is used to establish the correct diagnosis for people with Type 1 diabetes, and is highly predictive.  Diabetes researcher R. David Leslie MD says, "The best way to identify autoimmune diabetes is to assess diabetes-associated autoantibodies [GAD, IAA, IA-2, ZnT8], which represent the only relevant categorical trait."  An American Diabetes Association position statement affirms, “Consider measurement of pancreatic autoantibodies to confirm the diagnosis of Type 1 diabetes (Footnote 7).”

AAFP 2016:  Additional testing to determine the etiology of diabetes is not recommended.  Additional research is required to determine whether further testing [autoantibody testing] to classify the etiology of diabetes improves patient outcomes.  In the meantime, additional testing is not routinely recommended.

Fact:  There is an epidemic of misdiagnosis (T1D misdiagnosed as T2D), and misdiagnosis can result in the rapid onset of diabetic complications and even death due to diabetic ketoacidosis (DKA).  The Type 1 Diabetes Sourcebook (ADA/JDRF 2013) makes it clear that Type 1 and Type 2 diabetes are fundamentally different diseases (Footnote 8).  Without a doubt, a correct diagnosis would improve patient outcomes.  I challenge you to name even one disease where an incorrect diagnosis improves patient care or outcomes; I don’t believe there is one.    

For a patient with symptoms of diabetes, their first source of care probably is a family practice physician/primary care doctor.  Sadly, many of those doctors rely on the incorrect assumption that an adult with an elevated blood glucose must have Type 2 diabetes; autoantibody testing is a way to get beyond that assumption and actually provide a correct diagnosis.  If a person is positive for any one autoantibody and has a fasting blood glucose above 125 mg/dl, by definition the person has Type 1 autoimmune diabetes.  An article in Diabetes Spectrum, whose authors are associated with a university pharmacy college and who routinely encounter misdiagnosed patients, states, “It is imperative to establish distinct practice guidelines for the diagnosis and treatment of LADA [adult-onset Type 1 diabetes] and for providers to recognize this clinical scenario as one that requires special testing (autoantibody testing) to establish a proper diagnosis and thus improve patient safety and treatment efficacy.  Incorrect diagnosis can delay proper treatment (insulin therapy), exposing patients to potential adverse effects from ineffective Type 2 drugs, slowing progress toward normoglycemia, and ultimately increasing the risk of long-term complications (Footnote 9).”

In an editorial in American Family Physician, Jeff Unger MD states, “Family physicians care for most patients in the United States with Type 2 diabetes and, therefore, should be aware that approximately 10% of these patients have LADA [slowly progressive Type 1 diabetes] (Footnote 10).” Dr. Irl Hirsch states that “in the primary care setting, adult-onset Type 1 diabetes is not on the physician’s radar or in their bandwidth; they see so many Type 2s and have so little time.”  For primary care doctors who believe they have never misdiagnosed a person, I would suggest they consider what often happens in these situations: the frustrated patient seeks a second opinion, finally receives an accurate diagnosis and appropriate care, and never returns to the primary care provider who misdiagnosed them in the first place.  In this situation, the patient loses trust in the healthcare system, and the doctor never knows the original diagnosis was wrong.

The adult presentation of Type 1 diabetes does not present a challenge for the diabetes classification system—it is simply Type 1 diabetes.  The problem is that some in the medical community cannot let go of the myth that “Type 1 diabetes is a childhood disease,” and many in the medical profession have a difficult time coping with the fact that the majority of new-onset Type 1a diabetes is actually seen in adults.  If it were simply accepted that new-onset Type 1 diabetes occurs at all ages and is most commonly seen in adults (Footnote 11), then there undoubtedly would be fewer misdiagnosed cases.  However, we do know that scientific communities can be surprisingly resistant to new ideas or data that do not fit the accepted model, in this case the “juvenile diabetes” model.

Medical doctors already know how to effectively treat Type 1 diabetes in children and teenagers; that excellence in care should also be applied to adults with new-onset Type 1 diabetes.  When a child is diagnosed with Type 1 diabetes, the medical community springs to action on the child’s behalf, because Type 1 diabetes is a serious, life-threatening disease.  Kids who are diagnosed with Type 1 diabetes are shown great compassion, and the disease is acknowledged to be profoundly life-altering; adults deserve that same consideration.  When people with adult-onset Type 1 diabetes are finally correctly diagnosed and correctly treated with exogenous insulin (Footnote 12), they express great relief, and are able to reclaim their lives.

I would encourage the American Academy of Family Physicians to be at the forefront of addressing this epidemic of misdiagnoses—that would truly transform health care and achieve optimal health in alignment with your vision and mission.

Footnote 1: Slate magazine, March 6, 2018.  “Type 1 Diabetes is No Longer Just for Kids.”  Amy Mackinnon, author.

Footnote 2: Wall Street Journal, August 7, 2012.  “Wrong Call:  The Trouble Diagnosing Diabetes.”

Footnote 3: Slate magazine, March 6, 2018.  “Type 1 Diabetes is No Longer Just for Kids.”  Amy Mackinnon, author.

Footnote 4: July 13, 2016 Medscape article “New UK Prime Minister Brings Spotlight to Type 1 Diabetes.” Simon Heller, MD, and Irl B. Hirsch, MD, authors.

Footnote 5: S.R. Merger, R.D. Leslie, and B.O. Boehm.  “The broad clinical phenotype of Type 1 diabetes at presentation.”  Diabetic Medicine 2012.

Footnote 6: Miriam E Tucker, “Half of All Type 1 Diabetes Develops after 30 Years of Age.”  Medscape, September 20, 2016.  [Note that this study found that 50% of people diagnosed with Type 1 diabetes were diagnosed older than 30 years (and the study subjects only went up to 60 years, so greater than 50% are diagnosed over the age of 30)]. The Medscape article is based on data presented September 16, 2016, at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting by Dr Nicholas JM Thomas, of the Institute of Biomedical and Clinical Science, University of Exeter Medical School, United Kingdom (later published as Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. Lancet Diabetes Endocrinol. 2018 February; 6(2): 122-129).

Footnote 7: “Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association.”  Diabetes Care, June 16, 2014.  Jan L. Chiang, M. Sue Kirkman, Lori M.B. Laffel, and Anne L. Peters.

Footnote 8: “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, The Type 1 Diabetes Sourcebook.

Footnote 9: “Recognizing and Appropriately Treating Latent Autoimmune Diabetes in Adults (LADA)” (Diabetes Spectrum 2016 Nov; 29(4):249-252).

Footnote 10: The first medical journal article that described the 10% of Type 2s who are autoantibody positive and in fact have Type 1 diabetes was “Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents.”  The Lancet, Volume 309, No. 8020, p1025-1027, 14 May 1977.  Numerous subsequent studies, including the UKPDS, have confirmed the 10% figure.

Footnote 11: Miriam E Tucker, “Half of All Type 1 Diabetes Develops after 30 Years of Age.”  Medscape, September 20, 2016. 

Footnote 12: The Type 1 Diabetes Sourcebook (ADA/JDRF 2013) states, “For those presenting acutely as well as those presenting more indolently, starting insulin is the mainstay of therapy.”