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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basic premise of the thrifty gene hypothesis is that certain populations may have genes that determine increased fat storage, which in times of famine represent a survival advantage, but in a modern environment result in obesity and type 2 diabetes. The concept finds support in a unique animal model (Psammomys obesus) as well as among high type 2 diabetes susceptibility populations, such as North American Indians and South Pacific islanders. However, in some developing communities (e.g., Black South Africans) the thrifty phenotype hypothesis of perinatal malnutrition causing beta-cell dysfunction seems a better explanation, but this remains a contentious issue. Several genes have already been identified as candidates for the thrifty genotype, including those encoding proteins of the insulin-signaling and leptin pathways, as well as intermediary fat metabolism. Particular interest lies in the peroxisome-proliferator activated receptors. An innovative approach might be to focus on the "mirror image" of the thrifty genotype-congenital lipoatrophic diabetes mellitus, whose molecular defect remains enigmatic. We conclude that the genetic basis of the thrifty genotype probably derives from the multiplicative effects of polymorphisms at several sites mentioned above, rather than a single regulatory abnormality.
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PMID:The thrifty genotype in type 2 diabetes: an unfinished symphony moving to its finale? 986 47

Thirty-two patients with diabetes mellitus (22 IDDM and 10 NIDDM, 21 males and 11 females, age 44+/-11.8 years) were followed for 5.2+/-3.8 years after the onset of chronic renal failure, with the aim of evaluating the effect of low protein diets on the rate of decline of the residual renal function. During the 1.8+/-1.6 year follow-up period on free or uncontrolled low protein diet the mean rate of decline of creatinine clearance was 0.9+/-0.6 ml/min/month, significantly greater than that observed during 3.7+/-3.1 years on low or very low protein diets. The reduction of protein intake was followed by a significant decrease in daily urinary protein loss. A better glycaemic control was obtained on the low protein diet, and the daily insulin requirement decreased. The anthropometry, as well as the serum concentrations of rapid turnover proteins, did not change, in spite of the low or very low protein dietary supply for a long duration. The values of mean arterial pressure were quite similar during the follow-up period on free or uncontrolled low protein diet and during the study period on the low protein diet. A good compliance with reduced dietary intake (as demonstrated by the measurement of the daily urea excretion) was obtained in a large number of patients. In conclusion, our study confirms the protective effect on the residual renal function of low protein diets in IDDM and NIDDM patients with chronic renal failure due to diabetic nephropathy, in the absence of any sign of protein malnutrition.
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PMID:Dietary treatment of diabetic nephropathy with chronic renal failure. 987 Apr 26

Low birthweight is associated with insulin resistance, hypertension, coronary-artery disease, and non-insulin-dependent diabetes (NIDDM). A suggested explanation for this association is intrauterine programming in response to maternal malnutrition. We propose, however, that genetically determined insulin resistance results in impaired insulin-mediated growth in the fetus as well as insulin resistance in adult life. Low birthweight, measures of insulin resistance in life, and ultimately glucose intolerance, diabetes, and hypertension could all be phenotypes of the same insulin-resistant genotype. There is evidence to support this hypothesis. Insulin secreted by the fetal pancreas in response to maternal glucose concentrations is a key growth factor. Monogenic diseases that impair sensing of glucose, lower insulin secretion, or increase insulin resistance are associated with impaired fetal growth. Polygenic influences resulting in insulin resistance in the normal population are therefore likely to result in lower birthweight. Abnormal vascular development during fetal life and early childhood, as a result of genetic insulin resistance, could also explain the increased risk of hypertension and vascular disease. The predisposition to NIDDM and vascular disease is likely to be the result of both genetic and fetal environmental factors.
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PMID:The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. 1034 8

The 3 major components of the dyslipidemia of insulin resistance are increased triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and changes in the composition of low-density lipoprotein (LDL) cholesterol. Hyperinsulinemia and the central obesity that typically accompanies insulin resistance are thought to lead to overproduction of very low-density lipoprotein (VLDL) cholesterol. The result is more triglyceride-rich particles, fewer HDL particles, and more small, dense LDL. Postprandial triglyceride levels and measures of postprandial remnants also may contribute to increased coronary artery disease (CAD) risk in individuals with insulin resistance. Deficiency of lipoprotein lipase, an insulin-sensitive enzyme, might explain the abnormal levels of remnant particles in insulin resistance. The potential benefits of successful treatment of dyslipidemia are illustrated by clinical trials in patients with the dyslipidemia characteristic of insulin resistance (i.e., normal or only moderately elevated LDL, elevated VLDL, and low HDL). Both weight loss and exercise can improve insulin resistance and associated dyslipidemia. In patients with type 2 diabetes mellitus, certain antidiabetic therapies can also improve the lipid profile by improving insulin resistance.
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PMID:Insulin resistance and lipid metabolism. 1041 56

Type 2 diabetes is a heterogeneous disorder. Clinical expression of the disorder requires both genetic and environmental factors. One theory concerning its etiology is that it is the result of the evolution of a thrifty genotype that had survival benefits in the past but is detrimental in the current environment. An opposing theory is that it represents an adult metabolic response to fetal malnutrition. Hyperglycemia in type 2 diabetes results from absolute or relative insulin deficiency. Most often relative insulin deficiency is attributable to an inability to adequately compensate for insulin resistance. Insulin resistance may be caused by a variety of genetic or metabolic factors. The most common etiological factor in insulin resistance is central obesity. Insulin resistance is associated with a cluster of metabolic abnormalities that include glucose intolerance, hypertension, a unique dyslipidemia, a procoagulant state, and an increase in macrovascular disease. Clinical intervention studies have demonstrated that reduction in the chronic microvascular and macrovascular complications of type 2 diabetes requires treatment of hyperglycemia to achieve hemoglobin A1c <7.0%, blood pressure </=130/80 mmHg, and plasma LDL-cholesterol </=2.6 mmol/L (</=100 mg/dL). Oral antihyperglycemic agents increase endogenous insulin secretion, decrease insulin resistance, or lower postprandial plasma glucose rise by delaying absorption of complex carbohydrates. Long-term glycemic control in type 2 diabetes requires progressive, stepwise, combination treatment with oral agents and eventually combination treatment with oral agents and insulin.
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PMID:Type 2 diabetes: an overview. 1043 Aug 16

In a community based survey of gestational diabetes in 18 rural villages of the eastern zone of Tigray administrative region, northern Ethiopia, a total of 890 pregnant women with gestational age of 24 weeks and above were examined for gestational diabetes mellitus based on WHO criteria. A 75 gm oral glucose tolerance test was performed on each subject with measurement of glucose at 0 and 2 h. Blood glucose was determined by glucose oxidase method using capillary blood (Accutrend alpha, Boehringer Mannheim). The mean age of the mothers was 27.4 +/- 7.1 years. Forty four percent of the subjects were multiparas. The prevalence rate of gestational diabetes mellitus was found to be 3.7% (95% CI 2.5-4.9). The mean blood glucose 2 h after glucose load in those pregnant diagnosed to have gestational diabetes mellitus was 154.6 +/- 14.4 mg/dl (J.W. Rich-Edwards, G.A. Colditz, M.J. Stampfer, W.C. Willett, M.W. Gillman, C. Hennekens, F.E. Speizer, J.E. Manson, Birth weight and the risk for type 2 diabetes mellitus in adult women, Annu. Intern. Med. 130 (1999) 278-284). The prevalence of gestational diabetes mellitus in this region of the country is high as compared to other parts of Africa. The possible role and contribution of exposure of the general population in this area to chronic malnutrition as a result of prolonged famine, drought and war, to the high prevalence of gestational diabetes mellitus warrants further study.
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PMID:Prevalence of gestational diabetes mellitus in rural pregnant mothers in northern Ethiopia. 1062 91

The nutritional status, prenatally and early postnatally, plays a critical role in postnatal growth and development. Early malnutrition may change the original programming of organs, especially those in developmental phases, which can result in long-term changes in metabolism. The association between a low birth weight and the increased risk on type 2 diabetes, hypertension and cardiovascular disease is well known. In the present study we investigated whether intrauterine malnutrition or direct postnatal food restriction affects the onset of puberty in male and female rats. Intrauterine growth retardation (IUGR) was induced by uterine artery ligation on day 17 of gestation and postnatal food restriction (FR) by litter-enlargement to 20 pups per mother from day 2 after birth until weaning (24 d). Both models of malnutrition resulted in a persistent growth failure postnatally. The parameter of the onset of puberty was balano-preputial-separation (BPS) in the male rat and vaginal opening (VO) in the female rat. In both male IUGR (n = 26) and FR (n = 20) rats, the age at BPS was significantly delayed, with 48.1 +/- 1.9 d (p < 0.0001) and 50.4 +/- 2.9 d (p < 0. 0001), respectively, compared with controls (n = 30) with 45.8 +/- 1.4 d. In female IUGR rats (n = 37) the age at VO was significantly delayed, with 37.4 +/- 2.7 d (p < 0.04) compared with 36.1 +/- 1.5 d in controls (n = 23), but not in female FR rats (n = 18) with 36.5 +/- 2.2 d. Weight at onset of puberty did not differ between male IUGR and control rats, 194.5 +/- 20.0 g and 201.7 +/- 16.8 g, respectively, but was significantly lower in male FR rats with a weight of 175.6 +/- 17.5 g (p < 0.0001). In female IUGR as well as in female FR rats, weight at onset of puberty was significantly lower compared with controls: weight in IUGR 106.1 +/- 13.1 g (p < 0.001), weight in FR 85.3 +/- 7.6 g (p < 0.0001) and weight in controls 116.9 +/- 9.3 g. We conclude that early malnutrition, during late gestation or direct postnatally, results in a delayed onset of puberty in IUGR and FR male rats and in IUGR female rats, but not in FR female rats. The onset of puberty in these growth retarded rats as well as in controls does not depend on the achievement of a certain, crucial weight. The perinatal period appears to be a "critical time period" for the maturational process of pubertal development.
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PMID:The effects of intra-uterine growth retardation and postnatal undernutrition on onset of puberty in male and female rats. 1110 50

The number of cell divisions during embryonic and fetal life makes the embryo/fetus particularly vulnerable to effects resulting from exposure to an adverse intrauterine environment. Exposure to drugs and irradiation at this stage of development are able to cause congenital malformations and various cancers in later life. In-utero exposure to hyperglycaemia is able to lead to future diabetes that is heritable, but not genetic in origin. Fetal malnutrition causing growth restriction is able to lead to an increased risk of developing type 2 diabetes, hypertension and ischaemic heart disease in later life, especially if the growth restriction is followed by catch-up growth postnatally. This review discusses the various mechanisms by which these effects may occur, and presents the difficulties that will have to be faced if their world-wide health burdens are to be reduced.
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PMID:Long-term effects on offspring of intrauterine exposure to deficits in nutrition. 1112 90

Insulin controls glucose homeostasis by regulating glucose use in peripheral tissues, and its own production and secretion in pancreatic beta cells. These responses are largely mediated downstream of the insulin receptor substrates, IRS-1 and IRS-2 (refs 4-8), through distinct signalling pathways. Although a number of effectors of these pathways have been identified, their roles in mediating glucose homeostasis are poorly defined. Here we show that mice deficient for S6 kinase 1, an effector of the phosphatidylinositide-3-OH kinase signalling pathway, are hypoinsulinaemic and glucose intolerant. Whereas insulin resistance is not observed in isolated muscle, such mice exhibit a sharp reduction in glucose-induced insulin secretion and in pancreatic insulin content. This is not due to a lesion in glucose sensing or insulin production, but to a reduction in pancreatic endocrine mass, which is accounted for by a selective decrease in beta-cell size. The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance.
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PMID:Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. 1114 Jun 89

The Barker hypothesis states that there are foetal origins of adult disease. The hypothesis is primarily based on epidemiological associations between indicators of foetal malnutrition and mortality and morbidity in adulthood. The first association reported was between birth weight and coronary heart disease. Similar associations were found between birth weight and stroke, hypertension, type 2 diabetes mellitus, insulin resistance, serum lipids, and premature pubarche. In non-industrialized countries the associations appear to be even stronger. Although the Barker hypothesis has been criticized, the evidence from epidemiological studies and animal experiments appears sufficient to test it further and to consider the possible consequences for the physician. The first consequence could be that in taking a medical history from adults the physician should collect information about intrauterine growth. To facilitate this, communication between obstetricians, specialists in preventive child health care and paediatricians on the one hand and general practitioners and physicians on the other ought to be improved. A low birth weight, particularly smallness for gestational age, can be communicated to the adult patient as a potential risk factor for the diseases mentioned above and an extra reason to abstain from smoking and to avoid overweight.
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PMID:[Implications of the Barker hypothesis for general practitioners]. 1115 4


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