The Problem

It is time that the full scope of Type 1 diabetes is acknowledged, which includes millions of adults who are too frequently misdiagnosed as having Type 2 diabetes, an altogether different disease.

Monday, June 29, 2015

Early Insulin Therapy in Adult-Onset Type 1 Diabetes

There is substantial evidence that early insulin treatment preserves remnant beta cell mass, and also lowers the risk of complications and early death.  Sadly, complications and early death are more common amongst those with slowly progressive Type 1 diabetes (aka latent autoimmune diabetes in adults or LADA), as opposed to rapid-onset Type 1 diabetes, and I believe that is because of the lack of early, intensive treatment with insulin.  Medical doctors already know how to effectively treat Type 1 diabetes in children, teenagers, and young adults; that excellence in care should also be applied to adults with new-onset Type 1 diabetes (which of course includes LADA).

There is much debate about the timing and importance of initiation of insulin therapy in people with adult-onset autoimmune diabetes. LADA is defined as not requiring insulin for 6 months, but this is based on physicians’ clinical judgment not disease process and seems specious as Frederick Allen, before the discovery and first use of insulin on a patient with diabetes in 1922, kept Type 1 diabetics (many of them children) alive often for five years or more on a starvation (low carb) diet. Some scientists state that early insulin use has no advantages; yet patients with Type 1 report great relief in getting a correct diagnosis and insulin therapy because they feel so much better. Several published studies have shown that the misdiagnosed (Type 1s misdiagnosed as having Type 2 and not treated with insulin) have a much more rapid onset of diabetic complications. Rapid onset Type 1 diabetes should be treated by intensive insulin therapy as soon as possible; however, if a person has slowly progressive Type 1 diabetes, it is possible that exercise and a low carb diet can keep the person in control for some time. But insulin therapy should not be avoided due to fear.

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, personal communication).  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%), and the DCCT researchers stated, "Intensive [exogenous insulin] therapy for type 1 diabetes helps sustain endogenous insulin secretion, which, in turn, is associated with better metabolic control and lower risk for hypoglycemia and chronic complications" (Footnote 1).  Clearly, early intensive insulin therapy has enormous benefit.  LADA researchers in Japan (Kobayashi et al, 2002 (Footnote 2)) have conclusively demonstrated that better preservation of beta cell function occurs with exogenous insulin compared to sulfonylureas, and that sulfonylureas hasten beta cell destruction.  Researchers' results suggest that small doses of insulin effectively prevent beta cell failure in slowly progressive Type 1 diabetes, better glycemic control is achieved, and less proliferative retinopathy occurs (Footnote 3). In other words, doctors may inappropriately use Type 2 therapies (sulfonylureas) in new-onset Type 1 diabetes, but all scientific studies indicate that the correct therapy is intensive insulin therapy.

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).  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 diabetes and greatly reduce the risk of diabetic complications, thus making for a better life.

Some in the medical community believe that people with LADA can be treated initially with drugs for Type 2 diabetes (sulfonylureas).  The fact is that 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.  I also believe that there is irrational psychological thinking in effect (as opposed to evidence-based medicine), in which doctors/medical community want to believe that LADA is somehow different from childhood Type 1 diabetes, and they want to treat LADA as if it were Type 2 diabetes.  LADA is not Type 2 diabetes, it is a completely different disease, and people with LADA should not be treated as if they have Type 2 diabetes. Type 2 drugs (sulfonylureas) are not likely to be effective, in any case.  As stated in the Type 1 Diabetes Sourcebook (ADA/JDRF, 2013) “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 Type 1 Diabetes Sourcebook also says, “for those with early Type 1 diabetes, expert opinion recommends either low doses of basal insulin to prevent DKA or prandial insulin to prevent postprandial hyperglycemia.”

Dr. Richard Bernstein, author of The Diabetes Solution, believes the honeymoon can be prolonged indefinitely. He says (page 104): "Based upon my experience with the fair number of type 1 diabetics I've treated from the time of diagnosis, I'm convinced that the honeymoon period can be prolonged indefinitely. The trick is to assist the pancreas and keep it as quiescent as possible. With the meticulous use of small doses of injected insulin and with the essential use of a very low carbohydrate diet, the remaining capacity of the pancreas, I believe, can be preserved."

So in summary, there is substantial evidence that early, intensive insulin intervention preserves beta cells and prolongs the honeymoon.  It should be the standard of care for all people with new-onset Type 1 diabetes.

NOTE:  Some of the newer drugs for Type 2 diabetes may be beneficial for those with Type 1 diabetes.  Metformin is useful for those people with Type 1 diabetes who develop insulin resistance.  GLP-1 drugs and SGLT2 Inhibitor drugs may be beneficial.  But exogenous insulin is the standard of care for people with Type 1 diabetes.

Footnote 1:
Effect of Intensive Therapy on Residual β-Cell Function in Patients with Type 1 Diabetes in the Diabetes Control and Complications Trial: A Randomized, Controlled Trial.  Ann Intern Med. 1998;128(7):517-523. 

Footnote 2:
Kobayashi et al, 2002.  Insulin Intervention to Preserve β Cells in Slowly Progressive Insulin-Dependent (Type 1) Diabetes Mellitus.  Annals of the New York Academy of Sciences.  Volume 958, IMMUNOLOGY OF DIABETES: AUTOIMMUNE MECHANISMS AND THE PREVENTION AND CURE OF TYPE 1 DIABETES.  Pages 117–130.

Footnote 3:
Maruyama et al, 2003.  Multicenter prevention trial of slowly progressive Type 1 diabetes with small does of insulin (the Tokyo Study): preliminary report.  Ann NY Acad Scie, 2003 Nov; 1005:362-9.                                                                                                                         

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