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      Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth

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      Diabetologia

      Springer Science and Business Media LLC

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          Abstract

          Two follow-up studies were carried out to determine whether lower birthweight is related to the occurrence of syndrome X-Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia. The first study included 407 men born in Hertfordshire, England between 1920 and 1930 whose weights at birth and at 1 year of age had been recorded by health visitors. The second study included 266 men and women born in Preston, UK, between 1935 and 1943 whose size at birth had been measured in detail. The prevalence of syndrome X fell progressively in both men and women, from those who had the lowest to those who had the highest birthweights. Of 64-year-old men whose birthweights were 2.95 kg (6.5 pounds) or less, 22% had syndrome X. Their risk of developing syndrome X was more than 10 times greater than that of men whose birthweights were more than 4.31 kg (9.5 pounds). The association between syndrome X and low birthweight was independent of duration of gestation and of possible confounding variables including cigarette smoking, alcohol consumption and social class currently or at birth. In addition to low birthweight, subjects with syndrome X had small head circumference and low ponderal index at birth, and low weight and below-average dental eruption at 1 year of age. It is concluded that Type 2 diabetes and hypertension have a common origin in sub-optimal development in utero, and that syndrome X should perhaps be re-named "the small-baby syndrome".

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          Most cited references 17

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          Fetal and infant growth and impaired glucose tolerance at age 64.

          To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. Hertfordshire, England. 468 men born in east Hertfordshire and still living there. Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. 93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.
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            Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome.

            In a population-based survey of 2,930 subjects, prevalence rates for obesity, Type 2 (non-insulin-dependent) diabetes mellitus, impaired glucose tolerance, hypertension, hypertriglyceridaemia, and hypercholesterolaemia were 54.3, 9.3, 11.1, 9.8, 10.3 and 9.2%, respectively. The prevalence, however, of each of these conditions in its isolated form (free of the other five) was 29.0% for obesity, 1.3% for Type 2 diabetes, 1.8% for impaired glucose tolerance, 1.5% for hypertension, 1.0% for hypertriglyceridaemia, and 1.7% for hypercholesterolaemia. Two-by-two associations were even rarer. The large differences in prevalence between isolated and mixed forms indicate a major overlap among the six disorders in multiple combinations. In the isolated form, each condition was characterized by hyperinsulinaemia (both fasting and 2 h after oral glucose), suggesting the presence of insulin resistance. In addition, in any isolated condition most of the variables categorising other members of the sextet were still significantly altered in comparison with 1,049 normal subjects. In the whole of the subjects who presented with one or another disorder (1,881 of 2,930 or 64%), marked fasting and post-glucose hyperinsulinaemia was associated with higher body mass index, waist:hip ratio, fasting and post-glucose glycaemia, systolic and diastolic blood pressure, serum triglycerides and total cholesterol levels, and with lower HDL-cholesterol concentrations (all p less than 0.001). We conclude that (1) insulin sensitivity, glucose tolerance, blood pressure, body fat mass and distribution, and serum lipids are a network of mutually interrelated functions; and (2) an insulin resistance syndrome underlies each and all of the six disorders carrying an increased risk of coronary artery disease.
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              Hyperinsulinemia. A link between hypertension obesity and glucose intolerance.

               M Modan,  A Eshkol,  S Almog (1985)
              Hypertension and glucose intolerance, determined in a random population sample (n = 2,475), showed a highly significant (P less than 0.001) association from the mildest levels of both conditions, independent of the confounding effects of age, sex, obesity, and antihypertensive medications. Summary rate ratios for hypertension were 1.48 (1.18-1.87) in abnormal tolerance and 2.26 (1.69-2.84) in diabetes compared with normal tolerance. Altogether, 83.4% of the hypertensives were either glucose-intolerant or obese--both established insulin-resistant conditions. Fasting and post-load insulin levels in a representative subgroup (n = 1,241) were significantly elevated in hypertension independent of obesity, glucose intolerance, age, and antihypertensive medications. The mean increment in summed 1- and 2-h insulin levels (milliunits per liter) compared with nonobese normotensives with normal tolerance was 12 for hypertension alone, 47 for obesity alone, 52 for abnormal tolerance alone, and 124 when all three conditions were present. The prevalence of concentrations (milliequivalents per liter) of erythrocyte Na+ greater than or equal to 7.0, K+ less than 92.5, and plasma K+ greater than or equal to 4.5 in a subsample of 59 individuals with all combinations of abnormal tolerance obesity and hypertension was compared with those in 30 individuals free of these conditions. Altogether, 88.1% of the former vs. 40.0% of the latter group presented at least one of these three markers of internal cation imbalance (P less than 0.001). We conclude that insulin resistance and/or hyperinsulinemia (a) are present in the majority of hypertensives, (b) constitute a common pathophysiologic feature of obesity, glucose intolerance, and hypertension, possibly explaining their ubiquitous association, and (c) may be linked to the increased peripheral vascular resistance of hypertension, which is putatively related to elevated intracellular sodium concentration.
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                Author and article information

                Journal
                Diabetologia
                Diabetologia
                Springer Science and Business Media LLC
                0012-186X
                1432-0428
                January 1993
                January 1993
                : 36
                : 1
                : 62-67
                Article
                10.1007/BF00399095
                8436255
                © 1993

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