Correlates of Type 2 diabetes mellitus in children, adolescents and young adults in north India: a multisite collaborative case-control study.

AIMS: In this study we describe the clinical, anthropometric and biochemical characteristics of patients with early onset Type 2 diabetes mellitus (T2DM) (< 30 years of age) and compare them with healthy, non-diabetic individuals. METHODS: In this multisite collaborative study, 51 patients with T2DM (40 male, 11 female) and 69 non-diabetic individuals of similar age and gender distribution (controls) as the cases (46 male and 23 female) were investigated. The following parameters were measured; anthropometry [body mass index (BMI), waist circumference, waist-hip ratio (WHR) and skin-fold thickness at four sites], percentage body fat (%BF) and lipid profile. RESULTS: The mean (SD) age of diagnosis of T2DM was 21.4 (6.1) years. A significantly higher number of cases had a history of T2DM in first-degree relatives as compared with controls (82.3 vs. 23.2%, P < 0.001). The mean values and the prevalence of abnormal values of measures of generalized obesity (BMI and %BF) and abdominal obesity (waist circumference and WHR) were significantly higher in cases as compared with controls. Hypertriglyceridaemia [OR (95% CI): 4.6 (1.1-20.0)], high WHR [7.9 (2.5-24.4)] and family history of T2DM [7.3 (2.3-23.0)] were independently associated with T2DM. Age and gender adjusted odds ratios of T2DM were 23.3 (5.2-103.6), 37.7 (9.0-158.5) and 86.4 (17.0-438.5), respectively, with the following set of risk factors; hypertriglyceridaemia and high WHR, hypertriglyceridaemia and family history of T2DM, and high WHR and family history of T2DM. Finally, the presence of all three risk factors increased the odds of T2DM to 112.1 (10.8-1164.7). CONCLUSIONS: Early identification of the simple clinical, anthropometric and biochemical parameters which are strongly associated with early onset T2DM in young Asian Indians may be useful for primary prevention.

Study of the pituitary-thyroid functions at high altitude in man.

The alterations in serum levels of T3, T4, TSH and TBG, TSH response to 100 mug iv TRH, and urinary excretion of T3 and T4 were studied in 8 healthy men at sea level (SL), on days 1, 2, 4, 8 and 16 after arrival by air at high altitude (3,700 m, HA), and during days 5 to 7 after their return to SL. No significant alterations in serum levels of TSH and TBG or TSH response to TRH were observed during exposure to HA or on return to SL. There was, however, an acute elevation in both serum total T3 and T4. Serum total T3 from a mean basal+/-SE value of 128+/-13 ng/dl increased to 320+/-18 on day 1 and remained significantly elevated at 225+/-48 up to day 8 after arrival at high altitude. Similarly serum total T4 increased from basal level of 9+/-0.92 mug/dl to 15.2+/-1.2 and remained elevated till day 16 and it was 11+/-1.19 mug/dl during days 5 to 7 after return to SL. The urinary excretion of both T3 and T4 was decreased. These changes perhaps were the result of complex physiologic adjustments on acute exposure to high altitude, like shrinkage of the T3 and T4 distribution pools, altered binding capacities of thyroid hormones binding proteins, and a reduction in clearance of thyroid hormones from the plasma compartment; and were probably not suggestive of an enhanced thyroid activity. Their actual significance in high altitude adaptation in man is not clearly understood.

Metabolic responses to monocomponent human insulin infusions in normal subjects and patients with liver and endocrine disease.

Hypoglycaemic and growth hormone responses were studied at different steady-state plasma insulin concentrations during a graded infusion of monocomponent human insulin. The control group consisted of ten volunteer subjects. The other groups studied included women taking oral contraceptives and patients with obesity, thyrotoxicosis, myxoedema, acromegaly, diabetes mellitus (moderate and severe) and liver disease. The hypoglycaemic response was measured in two ways: (i) the percentage reduction in plasma glucose below basal, and (ii) the rate of fall of plasma glucose (Kg-%/min). Insulin sensitivity was greatest in the normal subjects and in the other groups decreased in the order thyrotoxicosis greater than oral contraceptive greater than obesity greater than myxoedema greater than acromegaly greater than liver disease. Insulin sensitivity was difficult to assess in the diabetic patients because basal plasma glucose concentrations were elevated. At any given insulin concentration, the diabetics metabolized approximately the same amount of glucose as the normal subjects but the fact that this rate of glucose turnover occurred at higher plasma glucose concentrations probably indicated insulin resistance. Within each group Kg at each dose level of insulin correlated with the steady state plasma insulin concentration during the same infusion period. Diminishing sensitivity to insulin was reflected in an increasing fasting plasma insulin and insulin/glucose ratio except in patients with diabetes. GH responses to insulin infusion in normal subjects reflected the pattern of fall of plasma glucose. In the diabetic patients GH secretion appeared to be related to the infusion of insulin and occurred before plasma glucose had fallen to hypoglycaemic levels. GH secretory patterns were within normal limits in women taking oral contraceptives and in seven of eleven patients with liver disease but were impaired in three of seven patients with thyrotoxicosis and four of five patients with myxoedema. Four obese patients had a markedly delayed but eventually normal GH response.

Insulin metabolism, insulin sensitivity and hormonal responses to insulin infusion in patients taking oral contraceptive steroids.

The metabolism of unlabelled human monocomponent insulin was studied in a group of six patients being treated with combined oestrogen-progestogen oral contraceptives (OC) and compared with a group of ten normal subjects. The parameters of insulin metabolism were determined by a priming dose-continuous infusion technique which enabled measurements of metabolic clearance rate (MCR) of insulin to be made at four separate steady state hormone concentrations spanning the physiological range. In normal subjects MCR was greatest at low insulin concentrations, falling from 24.7 ml/kg/min. at 16 muU/ml to 11.4 ml/kg/min. at a mean concentration of 280 muU/ml. In the OC group, MCR averaged 20.5 ml/kg/min. and did not change with increasing plasma insulin concentration. The plasma half-disappearance time (T 1/2) was longer than normal in the OC group (5.6 vs. 4.4 min., p less than 0.05) despite a higher MCR. The prolonged T 1/2 indicated that the apparent distribution space was increased in those on OC (166.6 vs. 82.7 mg/kg., p less than 0.0025). The results are interpreted as indicating increased capillary permeability to insulin and increased peripheral degradation. The fact that MCR did not fall in the OC group with increasing plasma insulin concentrations whereas it did in normal subjects, suggested that OC leads to the loss of saturable component of insulin degradation that is present in normal subjects. Insulin sensitivity (as judged by induced hypoglycaemia) was reduced in the OC group while growth hormone responses were within the normal range. Plasma cortisol was increased in those taking OC but the response to insulin induced hyperglycaemia was less marked than normal. The results indicate a significant alteration in insulin metabolism in these subjects, which may contribute to the impairment of carbohydrate tolerance seen in some women taking combined OC.

Extent of possible rehabilitation of service personnel with ischaemic heart disease.

Sixty unselected survivors from ischaemic heart disease, all male service personnel, were treated, within 1 to 6 months of recovery from the acute episode, by promotion of physical activity, correction of coronary risk factors, and routine use of nicoumalone and prenylamine lactate. The results showed that this approach was conducive to more rewarding rehabilitation than was obtained in 89 patients who, in the past, were on conventional treatment based on advice regarding weight, diet, and physical and mental activity. Thus within 1 to 30 months of treatment by this approach, out of 60 patients, 12 were fit for medical category A active service duties in operational areas in any part of the world in any terrain, including altitudes between 10,000 and 18,000 feet, 30 were fit for medical category B service duties in non-operational communication zones in any part of the world including altitudes below 10,000 feet, and 17 were fit for medical category C sedentary duties in non-operational areas in India only. One patient, who initially recovered from congestive heart failure, died while in a state of temporary unfitness for service. No patient was released from service on account of ischaemic heart disease. Against this, by the conventional approach, out of 89 patients, 81 were fit for medical category C sedentary duties in non-operational areas in India only, 4 were released from service, and 4 died.