June 26, 2002
Question from Etiwanda, California, USA:
Recently, my 14 year old son (5 feet 10 inches tall, 158 pounds), who has had type 1 diabetes since he was seven, has had higher A1cs (about 8.5%), and a blood test also showed that he is “insulin resistant”. I know this is common in people with type 2 diabetes and obesity. What causes the insulin resistance? How can he overcome it? Are there too many fats or proteins in his diet? We try to watch too many carbs. Does this happen due to his age and growth rate? Would the excess insulin that is needed due to the resistance cause cell changes (cancer) or kidney problems?
A blood test does not show insulin resistance so I am not certain what your health care team was referring to. One of the more common ways to assess for “insulin resistance” is to calculate how much insulin the person is receiving and compare that to the amount of insulin one might otherwise expect. There certainly are very sophisticated procedures to define the degree of insulin resistance.
In type 2 diabetes, the insulin resistance usually reflects being overweight. Those folks make insulin, but it doesn’t do the job efficiently; hence, “insulin resistance.” On the other hand, type 1 diabetes is a state of insulin deficiency. Nevertheless, some patients with type 1 diabetes who receive a lot of insulin are said to be “insulin resistant.” While this could be a true insensitivity to the effects of insulin, it more often reflects that patients are not following a meal plan closely, thus they are requiring more insulin to “cover the meal.” The increased amount of insulin, relative to what the health care team expects, can be deemed a relative insulin resistance.
As a general rule, teens may require about one to one and a half units of insulin for every kilogram of body weight. More than two units per kilogram certainly suggests some type of extra need for insulin, be it because of extra food or true insulin resistance. I should add that not uncommonly during puberty, the insulin requirements increase because of a number of factors including: pubertal hormones; the puberty growth spurt (which is often fueled by an enormous appetite –especially in a teenage boy!), changes in lifestyle, etc.
Additional comments from Dr. Tessa Lebinger:
I am not aware of any simple blood test that can diagnose insulin resistance in people on insulin. There is some data suggesting that in type 1 diabetes, there is a component of insulin resistance in addition to insulin deficiency, but this is determined by very sophisticated studies in research centers. At the present time there is no recommended treatment for the insulin resistance, but it is possible that this may change in the future. For more info see Greenfield JR, Samaras K, Chisholm DJ. Insulin resistance, intra-abdominal fat, cardiovascular risk factors, and androgens in healthy young women with type 1 diabetes mellitus.J Clin Endocrinol Metab 2002 Mar;87(3):1036-40.
Additional comments from Dr. Larry Deeb:
What test did they do? I don’t know how they documented the insulin resistance.
Additional comments from Dr. Donough O’Brien:
There are many causes of insulin resistance in childhood, most of them as yet not clearly understood, so it is hard to be precise about your son without knowing a lot more about his history and what tests defined ‘insulin resistance’.
As you point out, by far the most common cause is type 2 diabetes which is increasingly common in childhood and may be variably accompanied by other evidence for the ‘insulin resistance syndrome’ such as a strong family history, some increase in blood pressure, dyslipidemia and a skin condition called acanthosis nigricans. Your son however, though big for his age, has a BMI (Body Mass Index) of only about 23, which is comfortably short of obesity so I would doubt that he has a normal or slightly elevated serum C-peptide level to confirm this.
Because it is the most common form of diabetes in a seven year old, I think he almost certainly has type 1A (autoimmune) diabetes even though this may not have been confirmed at onset by positive antibody tests and recently by a negligible C-peptide serum level. A form of insulin resistance has been described in this group especially in the teen years. It is characterised primarily by high insulin requirements and increased blood triglycerides. A number of recent studies have suggested that Glucophage [metformin] is of value, and you should talk to your son’s diabetes team about this.
There is no evidence that insulin resistance increases the likelihood of cancer, but continued high serum insulin levels may predispose to changes in small blood vessels and thus ultimately to heart and kidney problems.
Additional comments from Dr. Linda DiMeglio:
No single blood test (that I am aware of) can diagnose insulin resistance in a child on insulin for type 1diabetes (since measured insulin levels reflect the most recent dose rather than any ambient level). If your doctors suspect insulin resistance, the diagnosis would more likely be made based upon the amount of insulin for his body weight he is receiving and/or physical exam findings.
I would clarify this before worrying about treatment options. Insulin resistance is not related to diet per se (although, as you have pointed out, it can be due to obesity). It can be related to adolescence (and the hormonal changes of that time), but this is normal for this part of puberty and only requires adjusting the insulin to meet the body’s increased needs.
[Editor’s comment: As already suggested by Dr O’Brien, recent discussion at the American Diabetes Association Scientific Sessions suggest that insulin resistance during puberty has a metabolic basis and may be improved with the use of metformin:
Jill Hamilton, Vera Zdravkovic, Elizabeth Cummings, Diane Finegood, Denis Daneman. Metformin Lowers HbA1c and Insulin Dose in Adolescents with Poorly Controlled Type 1 Diabetes. Diabetes 2002:51(S2):A427.
Metabolic control, measured by hemoglobin A1c (HbA1c) levels, tends to deteriorate in adolescents with type 1 diabetes (T1D), compared with younger children and adults. Insulin resistance (IR) peaks during puberty and is more pronounced in teens with T1D compared to nondiabetics. Our study aimed to determine whether the oral agent, metformin, used in combination with standard diabetes care, would (i) improve insulin sensitivity (Si) and (ii) lower HbA1c and insulin dose requirement. We performed a randomized, double-blind, placebo(P)-controlled 3 month trial of metformin (M) therapy in 27 adolescents with T1D, high insulin dose ([gt]1 u/kg/day) and high HbA1c ([gt]8%). At 0 and 3 mo., we measured (i) insulin sensitivity (Si) using frequently sampled IV glucose tolerance test (FSIGT) and (ii) clinical parameters of HbA1c, insulin dose (U/kg) and BMI.[br]At time 0, mean HbA1c was 9.2 [plusminus] 0.9%, insulin dose 1.2 [plusminus] 0.2 U/kg/day, BMI 24.2 [plusminus]3.9 kg/m2 with no difference between M and P groups. At 3 mo., the mean change in HbA1c was 0.6% lower in the M group compared to P (p [lt]0.05). This was achieved with lower insulin doses (M -0.14 [plusminus] 0.1 vs P + 0.02 [plusminus] 0.2 U/kg/day; p [lt] 0.05) and no significant change in BMI. Fasting glucose decreased significantly in the M group (p[lt]0.05). Si by FSIGT did not change significantly between the two groups; however, after adjustment for fasting glucose this approached significance (p = 0.07). One subject in the M group withdrew due to vomiting.[br]Variability in glucose excursions at the end of the FSIGT made Minimal Model analysis difficult to interpret. Modification of the FSIGT may be required in those with T1D and no residual insulin secretion. Thus, metformin treatment lowered HbA1c and insulin dose without weight gain in teens with T1D in poor metabolic control. It likely acts to improve Si, directly at the tissue level and indirectly by decreasing hepatic gluconeogenesis as well as by appetite suppression with weight loss. We conclude that metformin is safe and well tolerated and may represent a useful adjunct to standard T1D management in adolescents in poor metabolic control. Long-term studies are needed to determine whether these improvements are sustained.