Edavan P. Praveen

Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome.

Background and aim. Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women. Methods. In a case–control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion. Results. Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 ± 4.5 years (range 15–32 years) and their mean body mass index (BMI) was 19.7 ± 2.6 kg/m2. Mean blood glucose at 0, 1 and 2 h was 88.2 ± 7.2, 115.5 ± 25.5 and 91.8 ± 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 ± 1.1, 32.7 ± 26.5 and 14.6 ± 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 ± 3.1, 7.0 ± 3.1 and 11.4 ± 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 ± 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 ± 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m2 (mean 27.7 ± 6.3 kg/m2). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 ± 4.2, 2.0 ± 1.6 and 3.2 ± 3.5) than that of healthy controls. HOMA-IR was 3.1 ± 3.0. Conclusion. Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.

Gender Identity of Children and Young Adults with 5α-Reductase Deficiency

Male pseudohermaphroditism (46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last few decades. There is scant literature on this entity in India. We compiled data on five patients with this disorder. Four of our five patients were reared as females. Our assessment of these children reveals that they had male gender identity from childhood. Three of the four reared as females chose to change gender role at adolescence, while the fourth is still prepubertal. We conclude that all these patients had male gender identity from early childhood. The parents took note of this only after the appearance of male secondary sexual characteristics at puberty, thereby giving an impression of change in gender identity and gender role.

Morning cortisol is lower in obese individuals with normal glucose tolerance

Background There is no consensus on the role of cortisol in the pathogenesis of obesity and metabolic syndrome (MS). This cross-sectional study aimed to analyze the relationship of morning plasma cortisol and adrenocorticotropic hormone (ACTH) levels with body mass index (BMI) and glucose tolerance. Subjects and methods The sample frame was the “Offspring of individuals with diabetes study” database. A total of 358 offspring of individuals with type 2 diabetes mellitus (T2DM) and 287 individuals without a known family history of T2DM were recruited for the study. Subjects who were ≥10 years of age were selected from the database for analysis. Subjects with T2DM were excluded. All participants underwent a 75 g oral glucose tolerance test (OGTT), and blood samples were collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide. Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample. Results Four hundred and ninety-five participants (305 males [62%] and 190 females [38%]) were included in the analysis. ACTH and cortisol levels were higher in normal-weight subjects than in overweight/obese subjects. Both ACTH and cortisol increased as fasting plasma glucose increased. Cortisol levels were significantly lower in offspring of T2DM subjects with MS than in offspring of T2DM subjects without MS. When adjusted for BMI, the significance was marginal. In males, cortisol levels were negatively correlated with early insulin secretion during OGTT (insulinogenic index [0–30]) and positively with waist circumference and serum high-density lipoprotein cholesterol. In females, fasting glucose and systolic blood pressure were significantly and positively correlated. Conclusion Body weight was correlated negatively with morning plasma cortisol and ACTH, whereas fasting glucose was correlated positively.

Insulin sensitivity and β-cell function in normoglycemic offspring of individuals with type 2 diabetes mellitus: Impact of line of inheritance

Aims: The aim was to study the effect of family history of type 2 diabetes mellitus (T2DM) on insulin sensitivity and β-cell function in normoglycemic offspring. Material and Methods: Offspring of T2DM patients (cases) and individuals without family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent 75 g OGTT and samples were collected for plasma insulin, C-peptide, and proinsulin at 0, 30, 60, and 120 minutes. Results: A total of 271 cases (age 22 ± 10 years; 53% males) and 259 controls (28 ± 10 years, 66% males) were enrolled for the study. BMI, plasma insulin, C-peptide, proinsulin, HOMA-IR, and insulinogenic index (0-120) were significantly higher and whole-body insulin sensitivity (WBISI) and disposition index (0-120) [DI 120] were lower in cases compared to controls. After adjusting for BMI, proinsulin at 120 minutes, area under the curve (AUC) of proinsulin (during OGTT) and AUC proinsulin/AUC C-peptide were significantly higher in cases. Cases were subdivided into four groups according to inheritance pattern; paternal DM (PDM), maternal DM (MDM), grandparental DM (GPDM), and both parents DM (BPDM). The magnitude of differences varied with relationship (greater when both parents and grandparents were affected). Mean HOMA-IR was higher by 127% and 50% and DI 120 was lower by 33% and 18% (adjusted for age and gender) in the BPDM and GPDM groups respectively compared to controls. Conclusions: We observed higher BMI, plasma insulin, C-peptide, and proinsulin and lower insulin sensitivity and β-cell compensation in normoglycemic offspring of T2DM subjects compared to controls. Differences were greater when both parents and grandparents had T2DM.

Obesity and Metabolic Abnormalities in Offspring of Subjects with Diabetes Mellitus

BACKGROUND Some recent studies observed that a number of obese children had family members with type 2 diabetes. The aim of the present study was to assess prevalence of obesity and metabolic abnormalities among offspring of subjects with type 2 diabetes mellitus. METHODS Children of patients with type 2 diabetes mellitus were studied. Detailed medical history, physical examination, hemogram, renal and liver function tests, lipid profile, body composition, and oral glucose tolerance tests were done for all subjects. Plasma insulin was also done in addition to glucose at 0, 30, 60, and 120 min after oral glucose. RESULTS A total of 355 subjects from 208 families (194 males [55%] and 161 females [45%], mean age 23 +/- 11 years) were studied. Among them, 209 (58.9%) were lean, 91 (25.6%) were overweight, and 55 (15.5%) were obese. Seventeen (4.8%) subjects had impaired fasting glucose, 29 (8.2%) had impaired glucose tolerance, and 10 (2.8) had diabetes mellitus. Twenty (35.7%) of 56 with abnormal glucose tolerance were lean. One hundred six (29.8%) subjects had triglyceride levels greater than 150 mg/dL, 137 (38.6%) had low levels of high-density lipoprotein-cholesterol, and 67 (18.9%) had high total cholesterol levels. Prevalence of obesity, elevated plasma triglyceride, and glucose intolerance was higher among older subjects and subjects both of whose parents had diabetes. CONCLUSIONS Children from families with type 2 diabetes are at increased risk for obesity. Risk increases by fivefold when both parents have diabetes.

A case of autoimmune hypoglycemia outside Japan: Rare, but in the era of expanding drug-list, important to suspect

We are hereby reporting a case of a 72-year-old Indian man, who, in the absence of a detectable tumor, presented with symptomatic hypoglycemia in the postabsorptive state (3-5 h after meal). His serum levels of insulin and C-peptide were very high. He was not taking any hypoglycemic drug. Hypoglycemic episodes completely subsided after withdrawal of pentoprazole and incorporation of small frequent meals in the dietary plan. Six months after the initial presentation, the subject became free of hypoglycemic episodes. Although insulin autoimmune syndrome (IAS) is the third leading cause of spontaneous hypoglycemia in Japan, it is extremely uncommon in the Western Countries. Till 2009, more than 200 cases from Japan and as many as 58 cases outside Asia have been reported. To the best of our knowledge, this is the first case of IAS reported from India.

Plasma testosterone in adult normoglycaemic men: impact of hyperinsulinaemia.

This study analysed the relationship of plasma testosterone with β‐cell secretion, insulin sensitivity and other pituitary‐target gland hormones in normoglycaemic adult men. The sample frame was the ‘Offspring of individuals with diabetes study’ database. A total of 358 offspring of individuals with type‐2 diabetes (T2DM) and 287 individuals without known family history of T2DM were recruited for the study. Normoglycaemic men aged ≥18 years (maximum 55) were selected for this analysis. All participants underwent 75 g oral glucose tolerance test (OGTT); blood samples were collected at 0, 30, 60 and 120 min for plasma insulin and C‐peptide. Total testosterone, cortisol, adrenocorticotropic hormone, thyroid stimulating hormone and thyroxine (T4) were measured in the fasting sample. A total of 164 men (age 28 ± 7.7 years) were included in analysis. Testosterone correlated negatively with BMI, waist to hip ratio (WHR), area under curve (AUC) of C‐peptide and insulin (during OGTT) and was positively correlated with insulin sensitivity (r ~ 0.4). Cortisol and T4 positively correlated (weak) with testosterone (r ~ 0.2). In multivariate analysis, AUC C‐peptide, BMI, WHR (negatively) and cortisol (positively) were related to testosterone. Concluding, testosterone correlated negatively with BMI and β‐cell secretion. There was a positive association of testosterone with insulin sensitivity, cortisol and T4.

Morning plasma cortisol is low among obese women with polycystic ovary syndrome.

Abstract Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in women. It is associated with wide variety of metabolic disorders. The present study assessed morning plasma cortisol in women with PCOS. One hundred and ninety seven cases and 55 controls were enrolled for this study. The mean age of patients and controls were 23 ± 5.6 years and 25 ± 4.3 years. One hundred twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were significantly higher in lean PCOS women compared to controls (13.4 ± 5.1 versus 11.3 ± 4.5, p < 0.01) and over-weight PCOS women group (13.4 ± 5.1 versus 9.3 ± 3.2, p < 0.01). There was a trend for less acne and hirsutism with increase in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning plasma cortisol correlated negatively with BMI in PCOS women with normal glucose tolerance.