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Diabetes Care 28:2590a-2591, 2005
© 2005 by the American Diabetes Association, Inc.

Letters: Observations

Sex Differences of Age-Dependent Changes of Insulin Sensitivity in Japanese Nondiabetic Subjects

Michio Otsuki, MD1, Soji Kasayama, MD1, Hiroshi Saito, MD2, Mikio Mukai, MD2 and Masafumi Koga, MD2

1 Department of Medicine, Osaka University Hospital, Osaka, Japan
2 Department of Internal Medicine, Kinki Central Hospital, Itami, Japan

Address correspondence to Soji Kasayama, MD, Department of Medicine, Osaka University Hospital (C-4), 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail: kasayama{at}imed3.med.osaka-u.ac.jp

Impaired insulin sensitivity is associated with type 2 diabetes, hypertension, and atherosclerosis. This abnormality occurs by various causes such as genetic background, obesity, high-calorie diet, and low physical activity. Sex hormones also influence insulin sensitivity, which might be a cause for sex differences of the development of diabetes, hypertension, and atherosclerosis (1, 2). Collectively, however, there is no population-based study of sex differences in insulin sensitivity. Here, we aimed to determine whether there are sex and age differences of insulin sensitivity and insulin secretory activity in middle-aged nondiabetic subjects.

Of 1,934 Japanese subjects who visited the Kinki Central Hospital between April and October 2003 for their health examinations, we evaluated 1,395 subjects (854 men and 541 women) after exclusion of subjects with diabetes, malignant diseases, chronic or acute inflammatory diseases, elevated serum creatinine levels (≥106 µmol/l), autoimmune disorders, or subjects aged ≤40 years or ≥61 years.

Glucose tolerance status, homeostasis model assessment (HOMA) determinants (3), and BMI stratified by sex and age-groups (40–49 and 50–59 years) are shown in Table 1. Prevalence of impaired glucose tolerance was significantly higher in men than in women of both age-groups. In the 41–50 age-group, the index for insulin sensitivity (HOMA-%S) was higher in women than in men, whereas in the 51–60 age-group, there was no sex difference. The index for pancreatic ß-cell function (HOMA-%ß) was not different between men and women of both age-groups. BMI was lower in women than in men of both age-groups. In women, HOMA-%S was significantly higher in the 41–50 age-group than in 51–60 age-group (P = 0.0275), whereas in men it was lower in the 41–50 age-group than in the 51–60 age-group (P = 0.0348).


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  		Table 1— Glucose tolerance status, HOMA-%S, HOMA-%ß, and BMI in 1,395 Japanese nondiabetic subjects

 
We found that there were sex differences of age-dependent changes of insulin sensitivity, but not of insulin secretory activity, in Japanese nondiabetic subjects. Serum sex hormone levels differ between men and women, and in women, serum estrogens rapidly fall after menopause occurring around age 50. Therefore, sex hormones may be involved in the sex differences of age-dependent changes of insulin sensitivity. It has been reported that postmenopausal hormone replacement therapy lowered fasting glucose and insulin levels in nondiabetic women (4) and improved glycemic control in type 2 diabetic women (5), although disparate results have also been shown (6, 7). In men, serum testosterone levels have been shown to be inversely related to serum insulin level and BMI (8). In addition, it has been shown that androgens decreased the insulin-sensitizing adipocyte-derived protein adiponectin (9). Thus, as a whole, estrogens may have favorable effects on insulin sensitivity, whereas androgens may have undesirable effects on it.

In summary, insulin sensitivity depends on sex and age. Insulin sensitivity is higher in women than in men until age 50, but it falls to levels similar to men after age 50. Therapeutic strategies for eliminating insulin resistance for the prevention of diabetes and atherosclerosis should be classified by sex and age.

References

  1. Goodman-Gruen D, Barrett-Connor E: Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. Diabetes Care 23:912–918, 2000[Abstract]
  2. Galipeau DM, Yao L, McNeill JH: Relationship among hyperinsulinemia, insulin resistance, and hypertension is dependent on sex. Am J Physiol Heart Circ Physiol 283:H562–H567, 2002[Abstract/Free Full Text]
  3. Levy JC, Matthews DR, Hermans MP: Correct homeostasis model assessment (HOMA) evaluation uses the computer program (Letter). Diabetes Care 21:2191–2192, 1998[Medline]
  4. Barret-Connor E, Laakso M: Ischemic heart disease risk in postmenopausal women: effects of estrogen use on glucose and insulin levels. Arteriosclerosis 10:531–534, 1990[Abstract/Free Full Text]
  5. Friday KE, Dong C, Fontenot RU: Conjugated equine estrogen improves glycemic control and blood lipoproteins in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 86:48–52, 2001[Abstract/Free Full Text]
  6. Kimmerle R, Heinemann L, Heise T, Bender R, Weyer C, Hirschberger S, Berger M: Influence of continuous combined estradiol-norethisterone acetate preparations on insulin sensitivity in postmenopausal nondiabetic women. Menopause 6:36–42, 1999[Medline]
  7. Vehkavaara S, Westerbacka J, Hakala-Ala-Pietilä T, Virkamäki A, Hovatta O, Yki-Järvinen H: Effect of estrogen replacement therapy on insulin sensitivity of glucose metabolism and preresistance and resistance vessel function in healthy postmenopausal women. J Clin Endocrinol Metab 85:4663–4670, 2000[Abstract/Free Full Text]
  8. Phillips GB, Jing T, Heymsfield SB: Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metabolism 52:784–790, 2003[Medline]
  9. Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y: Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 51:2734–2741, 2002[Abstract/Free Full Text]

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This Article
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