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

This review summarized aspects of the widening scope, phenotypic expression, natural history, recognition, pathogeneses, and heterogenous nature of maturity-onset diabetes of the young (MODY), an autosomal dominant inherited subtype of NIDDM, which can be recognized at a young age. There are differences in metabolic, hormonal, and vascular abnormalities in different ethnic groups and even among Caucasian pedigrees. In MODY patients with low insulin responses, there is a delayed and decreased insulin and C-peptide secretory response to glucose from childhood or adolescence, even before glucose intolerance appears; it may represent the basic genetic defect. The nondiabetic siblings have had normal insulin responses for decades. The fasting hyperglycemia of some MODY has been treated successfully with sulfonylureas for more than 30 years. In a few, after years or decades of diabetes, the insulin and C-peptide responses to glucose are so low that they may resemble those of early Type I diabetes. The rate of progression of the insulin secretory defect over time does distinguish between these two types of diabetes. In contrast are patients from families who have very high insulin responses to glucose despite glucose intolerance and fasting hyperglycemia similar to those seen in patients with low insulin responses. In many of these patients, there is in vivo and in vitro evidence of insulin resistance. Whatever its mechanism, the compensatory insulin responses to nutrients must be insufficient to maintain normal carbohydrate tolerance. This suggests that diabetes occurs only in those patients who have an additional islet cell defect, i.e., insufficient beta cell reserve and secretory capacity. In a few MODY pedigrees with high insulin responses to glucose and lack of evidence of insulin resistance, an insulin is secreted which is a structurally abnormal, mutant insulin molecule that is biologically ineffective. No associations have been found between specific HLA antigens and MODY in Caucasian, black, and Asian pedigrees. Linkage studies of the insulin gene, the insulin receptor gene, the erythrocyte/Hep G2 glucose transporter locus, and the apolipoprotein B locus have shown no association with MODY. Vascular disease may be as prevalent as in conventional NIDDM. Because of autosomal dominant transmission and penetrance at a young age, MODY is a good model for further investigations of etiologic and pathogenetic factors in NIDDM, including the use of genetic linkage strategies to identify diabetogenic genes.
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PMID:Maturity-onset diabetes of the young (MODY). 268 21

10 patients with type 2 diabetes mellitus, in stable weight and diet therapy, followed a 2 months nutritional supplementation with guar, 15 g/day. Their previous nutritional and pharmacological therapy was not modified throughout the study. No changes occurred in body weight or major parameters of metabolic control. However, a significant fall occurred in fasting plasma, total and LDL cholesterol, and apolipoprotein B concentrations. Insulin sensitivity, measured by the "steady state plasma glucose", obtained after a 150 min glucose-insulin-somatostatin infusion, improved in all patients but two. A significant correlation was observed between steady state plasma glucose variations, the glycosylated haemoglobin A1c (r = 0.70; p less than 0.005), total (r = 0.77; p less than 0.001), and LDL cholesterol (r = 0.69; p less than 0.005) and apolipoprotein B concentrations (r = 0.75; p less than 0.005).
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PMID:[Effect of guar on plasma lipids and on the biological activity of insulin in patients with type 2 diabetes mellitus]. 282 61

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with elevated very-low-density lipoprotein (VLDL) triglyceride concentrations and abnormalities of low-density lipoprotein (LDL) composition. Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects, we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM. Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design. Medications, including antidiabetic therapy, were continued through the study. Compared with safflower oil treatment, fish oil supplementation resulted in a significant reduction of total plasma triglycerides of 24% at the 4-g dose and a larger reduction of 39% at the 7.5-g dose. These decreases were due to similar reductions in VLDL triglycerides. LDL cholesterol levels were mildly elevated, but a larger 20% increase in LDL apolipoprotein B (apoB) concentration was observed. During supplementation with the fish oil concentrate, the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values, but not when compared with safflower oil treatment. High-density lipoprotein (HDL) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment. At the 7.5-g dose, fasting glucose and glycohemoglobin levels increased by 20 and 12%, respectively, but were unchanged at the lower level of supplementation. Thus, in NIDDM patients, dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of fish oil concentrate on lipoprotein composition in NIDDM. 318 46

The clinical efficacy of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitor simvastatin in the treatment of hypercholesterolaemia in non-insulin-dependent diabetes (NIDDM), was examined in a double-blind placebo-controlled study of 6 months in 70 patients with NIDDM (age 25-70 years), of whom 57 were randomised to placebo (29 patients) or simvastatin for 6 months, following a 3-month run-in on diet. Patients were hypercholesterolaemic (7.8 (7.6-8.0) (mean (95% confidence intervals)) mmol/l simvastatin vs. 8.0 (7.7-8.5) mmol/l placebo) and mildly hypertriglyceridaemic (2.6 (2.2-3.0) simvastatin vs. 2.9 (2.3-3.5) placebo). Other lipid measures and estimates of glycaemic control and haemostasis were similar in both groups. There were no significant changes in lipids, haemostatic factors, or measures of glycaemic control in the placebo treatment group. Conversely by the end of 24 weeks, simvastatin produced a 28% reduction in cholesterol (to 5.6 (5.0-6.2) mmol/l (P < 0.001)), a 38% reduction in LDL cholesterol (from 5.5 (5.4-5.6) mmol/l to 3.4 (2.8-4.0) mmol/l, P < 0.001), a 15% reduction in triglyceride (to 2.2 (1.8-2.6) mmol/l, P < 0.05, and a 9% rise in HDL (from 1.16 (1.07-1.25) to 1.23 (1.14-1.32) mmol/l, P < 0.05). Improvements in apolipoprotein B (apo B) (-28%, P < 0.001), the LDL cholesterol to apo B ratio (-20%, P < 0.001), and apo A1 (+15%, P < 0.001) were recorded. There were no effects upon fibrinogen, factor VII activity, factor VIII activity, or measures of glycaemic control (fasting glucose, insulin, C-peptide, or HbA1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Simvastatin in non-insulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures. 807 Mar 2

In families of subjects with premature ischaemic cerebrovascular attacks (a total of 45 families with 190 members) the authors detected a high incidence of dyslipidaemia, arterial hypertension, impaired glucose tolerance and non-insulin dependent diabetes mellitus, frequently with striking cumulation. The authors investigated therefore the relationship of the insulin level as an indirect reflection of insulin resistance with these risk factors. The fasting insulin levels correlated significantly positively with triglyceride levels, apolipoprotein B, atherogenic indices and negatively with HDL-cholesterol. The probands and siblings with arterial hypertension had significantly higher fasting insulin levels, as compared with subjects without hypertension which was due to a more frequent incidence of overweight. Patients with an impaired glucose tolerance and NIDDM had significantly higher fasting insulin levels and insulin levels after two hours (the latter value was not assessed in diabetes) and unfavourable "atherogenic" lipid and lipoprotein values, as compared with subjects without glucose intolerance and the control group. Overweight (BMI > 26) had an adverse impact on all investigated indicators of lipid and carbohydrate metabolism whereby a W/H ratio > 0.85 as a manifestation of central obesity further accentuated this adverse effect. The authors draw from these results therapeutic conclusions as regards the mentioned risk factors in these families. They emphasize the importance of non-pharmacological intervention of the metabolic X syndrome by weight reduction and more physical activity not only in families of subjects with early atherosclerosis but in the entire population which has a high prevalence of cardiovascular diseases.
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PMID:[Reaven's metabolic syndrome X in the families of individuals with premature cerebrovascular attacks]. 821 22

The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2% +/- 2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of XbaI cleavage site). Patients with the X1 allele (absence of XbaI cleavage site) tended to have a higher frequency of macroangiopathy, although the differences were not statistically significant. There was no difference in the prevalence of microangiopathy between the groups. In subjects with only an R1 allele (= R+; homozygous for the presence of EcoRI cleavage site) the prevalence of coronary heart disease (CHD) was observed to be high (61.9%) as compared to the subjects possessing an R2 allele (= R-; homozygous or heterozygous for the absence of the EcoRI cleavage site) (46.7%; p < 0.02). When the polymorphisms XbaI (subjects homozygous for the absence of the cutting site = X+; subjects homozygous or heterozygous for the presence of the cutting site = X-) and EcoRI were combined, the prevalence of macroangiopathy was observed to be high in X+R+ (80.0%) as compared with X+R- (44.2%), X-R+ (56.8%) and X-R- (50.0%) (p < 0.03). The prevalence of macroangiopathy tended to be particularly high in patients with the apoprotein E4 allele (phenotype E4/4 or E4/3), combined with either X+ or R+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein B gene DNA polymorphisms are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus. 826 46

Lipoprotein(a) (Lp(a)) consists of a unique apolipoprotein, apolipoprotein(a), (apo(a)) linked by a disulphide bridge to apolipoprotein B of low density lipoprotein (LDL). Apo(a) is homologous with plasminogen and exhibits genetic polymorphism with the commoner phenotypes due to larger forms being associated with lower plasma levels and the less common phenotypes associated with smaller forms and higher plasma levels. The later are more common in patients with macrovascular disease. In a study of 6448 patients with established coronary heart disease we found that 43% had apo(a) levels above 300 units/litre and 10% had levels above 1000 units/litre and a geometric mean of 201 units/litre in contrast to 140 normal controls in whom 25% exceeded 300 units/litre, 1% exceeded 1000 units/litre and the geometric mean was 107 units/litre. Amongst patients with cholesterol levels < 5.5 mmol/L undergoing coronary artery surgery were patients with low HDL levels and raised apo(a) levels who would not be identified in screening focusing primarily on total cholesterol. In patients with both insulin dependent and non insulin dependent diabetes mellitus those with microalbuminuria or albuminuria (known to be at high risk for macrovascular disease) had apo(a) levels comparable to non diabetic patients with coronary artery disease while diabetic patients without microalbuminuria had normal levels of apo(a). It is likely that apo(a) has a role in the accelerated macrovascular disease in diabetic patients with renal disease.
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PMID:Apolipoprotein(a) and atherogenesis. 826 49

Lipoprotein composition was determined using ultracentrifugation in 20 non-insulin-dependent (NIDDM) diabetic patients on diet only (D), 20 NIDDM patients on diet and sulfonylurea therapy (T), and 20 nondiabetic control subjects (C), all of whom had total plasma cholesterol concentrations < 6.5 mmol/L and total plasma triglyceride concentrations < 3.0 mmol/L. Although the groups were well matched for age, body mass index, total triglyceride levels, and total cholesterol concentrations, there were significant compositional abnormalities in the low-density lipoprotein (LDL) fractions of diabetic subjects. The LDL total lipid to apolipoprotein B weight ratio (representing the density distributions of LDL particles) was reduced in both diabetic groups: 3.75 +/- 0.3, 3.50 +/- 0.28, and 3.54 +/- 0.22 in C, D, and T groups, respectively (mean +/- SD; P < .05). This was associated with a significant shift in the hydrated density distributions of LDL in the diabetic groups, with the average peak densities being 1.0320 g/mL (in C), 1.0365 g/mL (in D), and 1.0380 g/mL (in T) (P < .05). The LDL particles were also smaller in the NIDDM patients: 21.1 +/- 0.7, 20.4 +/- 0.5, and 20.6 +/- 0.5 nm in C, D, and T groups, respectively (P < .05). When the NIDDM groups were analyzed together, the LDL peak density was found to correlate with both insulin resistance (measured by a modified Harano technique; r = 0.37, P < .015) and total triglyceride concentrations (r = 0.40, P < .01). The results show that diabetic patients have small, dense LDL particles, which may be related to insulin resistance, and that these occur with minimal elevations of total triglyceride concentrations. These potentially atherogenic changes may contribute to the increased coronary heart disease in diabetic patients with mild hyperlipidemia.
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PMID:Lipoprotein compositional abnormalities and insulin resistance in type II diabetic patients with mild hyperlipidemia. 831 6

Altogether 86 patients with recently diagnosed NIDDM, aged 40-64 years were randomised after 3 months of basic education to intensified diet (Int. group, 21 men, 19 women) or conventional treatment groups (Conv. group, 28 men, 18 women). The aim was to examine whether an intensified diet education would result in a better metabolic control and greater reduction in cardiovascular risk factors than conventional treatment for obese patients with recently diagnosed type 2 diabetes mellitus. Furthermore, both groups were re-examined after a second year of observation period to find out the maintenance of the results after intervention. After basic education, Int. group participated in 12-months diet education, while Conv. group was treated in local health centres. During the intervention period, only Int. group showed further weight reduction. Only 20% of patients in Int. and 6% of patients in Conv. group had BMI < 27 kg/m2 at the end of the intervention, while 75% of patients in Int. and 52% of patients in Conv. group had achieved a good metabolic control (fasting blood glucose < 6.7 mmol/l; P = 0.005 between groups). Serum total cholesterol did not change significantly, but the changes in HDL-cholesterol, triglycerides and apolipoprotein B level were significant in Int. group only. The proposed acceptable values for serum lipids were achieved by 52 to 88% of patients without major differences between the two groups. During the second year of observation, weight gained in both groups and a deterioration was seen in metabolic control. Despite that a greater proportion of patients in the Int. group still was in good metabolic control (55.3% vs. 31.8%, P = 0.016), furthermore Int. group was receiving less frequently oral drugs for hyperglycaemia than Conv. group. No differences in serum lipids were observed between the groups after the observation period. HDL-cholesterol showed a persistent improvement in both groups.
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PMID:The maintenance of improved metabolic control after intensified diet therapy in recent type 2 diabetes. 831 21

NIDDM and the metabolic syndrome are characterized by a low serum, HDL cholesterol content and a high triglyceride level, whereas total and LDL cholesterol concentrations are not necessarily elevated. Variable results have been reported on cholesterol absorption, elimination, and synthesis in NIDDM, but no studies are available on subjects within the normal range of blood glucose. From serum samples collected in 1985 from 203 nondiabetic men aged 51-66 years, we examined lipids, cholesterol precursors (reflecting cholesterol synthesis), and plant sterols and cholestanol (reflecting cholesterol absorption) in relation to fasting blood glucose. The findings prompted us (in 1993) to further examine 11 men from the highest and lowest glucose thirds of 203 nondiabetic men by additional dietary, serum, and fecal analyses for absorption, elimination, and synthesis of cholesterol and insulin sensitivity. In 1985, blood glucose was significantly related to LDL apolipoprotein B (P = 0.05) but not to LDL cholesterol (P = 0.19). Significantly higher serum lathosterol and desmosterol-to-cholesterol proportions and lower plant sterol and cholestanol proportions in the highest rather than the lowest glucose thirds suggested that the subjects with high normal blood glucose had decreased absorption and enhanced synthesis of cholesterol. In 1993, men with the lowest glucose versus those with the highest glucose had a lower waist-to-hip ratio, plasma HbA1c, fasting and postload insulin and glucose values, and a higher insulin sensitivity index. In agreement with the 1985 non-cholesterol sterol data, direct analyses of cholesterol metabolism showed further higher cholesterol absorption efficiency (P = 0.03) and serum plant sterol and cholestanol proportions (P < 0.001). Despite a slightly lower dietary cholesterol intake, cholesterol synthesis (P = 0.02) and serum lathosterol (P < 0.01) and desmosterol (P < 0.01) proportions were lowest in men with the lowest glucose third. We conclude that noncholesterol sterols in serum exhibits a long-lasting correlation with blood glucose level in a nondiabetic male population. Low intestinal absorption and high synthesis of cholesterol characterize men with high normal blood glucose. Differences in cholesterol metabolism could be due to underlying insulin effects associated with obesity-like fat distribution and may thus imply novel aspects in the metabolic interrelation between insulin and cholesterol in humans.
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PMID:Associations of fasting blood glucose with cholesterol absorption and synthesis in nondiabetic middle-aged men. 863 49


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