Between Men and Women With Type 1 Diabetes

The aim of this study was to determine whether s e x-related differences occur in counterregulatory responses to hypoglycemia in adult type 1 diabetic patients. Experiments were carried out on 16 (8 men/8 women) type 1 diabetic patients and compared with 16 (8 men/8 women) ageand weight-matched normal individuals. Men and women with type 1 diabetes were matched for age (26 ± 2 vs. 25 ± 1 years), duration of diabetes (9 ± 1 vs. 8 ± 1 years), glycemic control (HbA1 c 7.7 ± 0.3 vs. 7.8 ± 0.2%), and weight (BMI 22.8 ± 1 vs. 22.1 ± 1 k g / m), respectively. After normalizing plasma glucose overnight, patients underwent a 2-h hyperinsulinemic-hypoglycemic clamp study. Plasma glucose (3.0 ± 0.1 mmol/l) and insulin (510 ± 48 pmol/l) levels were equated in all groups. Plasma epinephrine, norepinephrine, growth hormone (GH), muscle sympathetic nerve activity (MSNA), and endogenous glucose production (EGP) responses were significantly lower (P < 0.01) in type 1 diabetic women compared with men. Autonomic symptom scores, lipid oxidation, none s t e r i fied fatty acids (NEFAs), and glycerol responses were equivalent between men and women with type 1 diabetes despite significantly reduced sympathoadrenal and MSNA responses in women. Autonomic n e r v o u s system (ANS) and EGP responses were equivalent in t y p e 1 diabetic and normal individuals. However, lipid oxidation (assessed by indirect calorimetry), glycerol, and NEFA responses were increased (P < 0.01) in t y p e 1 diabetic patients compared with normal control subjects. We conclude that counterregulatory responses to fixed hypoglycemia differ markedly in men and women with type 1 diabetes: 1 ) sympathetic n e r v o u s system, GH, and EGP responses are significantly reduced in type 1 diabetic women, 2) autonomic symptom awareness and lipolytic responses appear to be relatively increased in type 1 diabetic women compared with men, and 3) during conditions of similar hyperinsulinemic hypoglycemia and ANS drive, lipid oxidation and lipolytic responses can be increased in type 1 diabetic patients compared with normal individuals. Diabetes 4 9 :6 5–72, 2000 Recent studies have demonstrated that a wide spectrum of neuroendocrine counterregulatory responses to hypoglycemia are reduced in healthy young women (1–4). Included in this array of altered responses are the key counterregulatory hormones glucagon and epinephrine (EPI). These findings tend to explain why plasma glucose levels fall to a lower level during fasting in women (5). If a similar spectrum of reduced neuroendocrine counterregulatory responses exist in women with type 1 diabetes, then an increased incidence of hypoglycemia might be expected in these individuals. However, data from the Diabetes Control and Complications Trial demonstrate that the frequency of hypoglycemia is sex neutral in t y p e 1 diabetes (6). This finding appears somewhat incongruous with data on normal women and poses the question whether counterregulatory responses to hypoglycemia are similar in healthy and type 1 diabetic women. To date, virtually no data are available examining the effects of sex on hypoglycemic counterregulation in type 1 diabetic adults. Arslanian et al. (7) investigated the effects of sex in a group of adolescents with type 1 diabetes. Interestingly, these authors reported that neuroendocrine counterregulatory responses were similar or even increased (growth hormone [GH]) in adolescent females with type 1 diabetes compared with age-matched type 1 diabetic males. In the study of Arslanian et al., glucose levels were not controlled but allowed to fall freely after cessation of a hyperinsulinemiceuglycemic clamp. Because of differences in insulin sensit i v i t y, glucose levels were significantly lower in males, and thus a comparison of counterregulatory responses at equivalent hypoglycemia between sexes appears to be lacking in t y p e 1 diabetic patients. Therefore, the aim of this study is to determine whether neuroendocrine, metabolic, and autonomic nervous system (ANS) responses to fixed equivalent hypoglycemia differ in men and women with type 1 diabetes.