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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Not all patients with diabetes develop clinically significant nephropathy and, for this reason, attention has begun to focus on the risk factors for development of this serious complication. These risk factors have not been quantified to the same degree as those factors associated with more common progressive vascular diseases, such as atherosclerosis. However, studies of pathogenesis and clinical and epidemiological surveys of diabetic nephropathy point to numerous risk categories. Glycemic control, genetic and familial predispositions, renal and glomerular enlargement, glomerular hyperfiltration, and capillary and systemic hypertension can be invoked as contributors to this disease process. This review focuses on hemodynamic alterations and their role in the development and progression of diabetic nephropathy. Increases in GFR, largely driven by increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM. This abnormality of renal vascular control probably is derived from alterations in several vasoactive control systems. In addition, the elevations in capillary pressure may be damaging to the glomerular capillaries. Arterial hypertension is not necessarily present before clinical nephropathy appears; however, it is a usual concomitant of progressive diabetic renal disease. The strongest evidences for the roles of altered systemic and renal hemodynamics in the progression of diabetic renal disease are clinical and experimental studies demonstrating attenuation of the disease process by lowering systemic and capillary pressures with antihypertensive agents, and dietary and glycemic modifications. Thus, although multiple factors probably interact to determine risk for the development of diabetic nephropathy, hemodynamic forces are a particularly important contributor and are especially amenable to therapeutic intervention.
Diabetes Care 1992 Sep
PMID:Diabetic nephropathy. Metabolic versus hemodynamic considerations. 139 17

NIDDM patients have a two- to fourfold increased risk of CHD relative to nondiabetic subjects. This excess risk is explained only partially by increased levels of standard risk factors. We compared the plasma concentrations of Lp(a) in NIDDM patients (n = 260) and nondiabetic subjects (n = 336) who participated in a population-based study (San Antonio Heart Study). Lp(a) was measured using a monoclonal anti-Lp(a) antibody. NIDDM patients and nondiabetic subjects had similar Lp(a) concentrations for both men (13.6 +/- 1.5 vs. 16.1 +/- 1.4 mg/dl) and women (12.6 +/- 0.8 vs. 15.9 +/- 1.3 mg/dl) (P = 0.361). Duration of diabetes and level of fasting glycemia were not significantly related to Lp(a) concentrations. Lp(a) levels were significantly higher in patients who had higher total and LDL cholesterol levels. We conclude that in a large population-based study, Lp(a) levels are not increased in NIDDM patients.
Diabetes 1992 Oct
PMID:Lp(a) concentrations in NIDDM. 139 99

Previous studies indicate that diets rich in digestible carbohydrates improve glucose tolerance in nondiabetic individuals, but may worsen glycemic control in NIDDM patients with moderately severe hyperglycemia. The effects of such high-carbohydrate diets on glucose metabolism in patients with mild NIDDM have not been studied adequately. This study compares responses to an isocaloric high-carbohydrate diet (60% of total energy from carbohydrates) and a low-carbohydrate diet (35% of total energy from carbohydrates) in 8 men with mild NIDDM. Both diets were low in saturated fatty acids, whereas the low-carbohydrate diet was rich in monounsaturated fatty acids. The two diets were matched for dietary fiber content (25 g/day). All patients were randomly assigned to receive first one and then the other diet, each for a period of 21 days, in a metabolic ward. Compared with the low-carbohydrate diet, the high-carbohydrate diet caused a 27.5% increase in plasma triglycerides and a similar increase in VLDL-cholesterol levels; it also reduced levels of HDL cholesterol by 11%. Plasma glucose and insulin responses to identical standard breakfast meals were studied on days 4 and 21 of each period, and these did not differ significantly between the two diets. At the end of each period, a euglycemic hyperinsulinemic glucose clamp study with simultaneous infusion of [3-3H]glucose revealed no significant changes in hepatic insulin sensitivity; and peripheral insulin-mediated glucose disposal remained unchanged (14.7 +/- 1.4 vs. 16.5 +/- 2.3 microM.kg-1.min-1 on the high-carbohydrate and low-carbohydrate diets, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Oct
PMID:Comparison of effects of high and low carbohydrate diets on plasma lipoproteins and insulin sensitivity in patients with mild NIDDM. 139 1

Glucokinase, the major enzyme that phosphorylates glucose upon entry into liver and islet beta-cells, has been considered a prime candidate for inherited defects predisposing to NIDDM. Now that the human gene has been isolated, this question has been addressed directly. Polymorphic markers flanking the gene were identified. These markers (microsatellites) are composed of variable numbers of dinucleotide repeats that vary in size, resulting in different alleles. Variably sized alleles can be typed rapidly from genomic DNA of individuals by the PCR. Studies of inheritance of glucokinase genes have revealed significant linkage in families with early-onset NIDDM, or MODY, and mutations have been identified within the coding region of the gene in some families. These studies are extremely encouraging, as they indicate that genes can be identified even in this heterogeneous genetic disorder. This study considers the phenotypes that result from glucokinase defects and the relationship of MODY to NIDDM, and it estimates the role of glucokinase defects in NIDDM in general.
Diabetes 1992 Nov
PMID:Glucokinase and NIDDM. A candidate gene that paid off. 139 13

NEFAs characteristically are elevated in obese NIDDM patients in both the basal state and after insulin. This elevation might aggravate glycemic control both by decreasing peripheral glucose disposal (glucose-fatty acid cycle), and by increasing HGO. Thus, lowering plasma NEFA levels might improve carbohydrate metabolism. We therefore measured HGO and fuel use (by indirect calorimetry) both in the basal state and during the last 30 min of a hyperinsulinemic clamp (0.025U.kg-1.h-1) in 8 obese NIDDM patients (BMI 34.8 +/- 1.0 kg/m2) after complete overnight suppression of plasma NEFA levels with acipimox, a new nicotinic acid analogue. After acipimox, mean basal plasma NEFA and glycerol levels were lower than control values (0.11 +/- 0.02 vs. 0.65 +/- 0.04 mM, P < 0.001; and 16 +/- 3 vs. 68 +/- 7 microM, P = 0.004, respectively) and were accompanied by a fall in lipid oxidation (acipimox vs. placebo: 16.1 +/- 1.2 vs. 38.8 +/- 2.4 mg.m-2 x min-1; P < 0.001) and a rise in glucose oxidation (91.1 +/- 6.2 vs. 54.1 +/- 9.0 mg.m-2 x min-1; P = 0.002). Basal HGO and fasting plasma glucose levels were lower (94.1 +/- 9.2 vs. 118.5 +/- 9.5 mg.m-2 x min-1, P = 0.01; and 8.3 +/- 1.2 vs. 9.8 +/- 1.2 mM; P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Nov
PMID:Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects. 139 16

A spontaneously diabetic rat with polyuria, polydipsia, and mild obesity was discovered in 1984 in an outbred colony of Long-Evans rats, which had been purchased from Charles River Canada (St. Constant, Quebec, Canada) in 1982. A strain of rats developed from this rat by selective breeding has since been maintained at the Tokushima Research Institute (Otsuka Pharmaceutical, Tokushima, Japan) and named OLETF. The characteristic features of OLETF rats are 1) late onset of hyperglycemia (after 18 wk of age); 2) a chronic course of disease; 3) mild obesity; 4) inheritance by males; 5) hyperplastic foci of pancreatic islets; and 6) renal complication (nodular lesions). Histologically, the changes of pancreatic islets can be classified into three stages: 1) an early stage (6-20 wk of age) of cellular infiltration and degeneration; 2) a hyperplastic stage (20-40 wk of age); and 3) a final stage (at > 40 wk of age). These clinical and pathological features of disease in OLETF rats resemble those of human NIDDM.
Diabetes 1992 Nov
PMID:Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. 139 18

Four overlapping DNA fragments spanning 32 kb containing the human GLUT4 facilitative glucose-transporter gene were isolated and characterized. The sequence of the GLUT4 gene (approximately 6.3 kb) and 2.0 kb of the promoter region was determined. The sequence of the promoter revealed potential binding sites for transcription factors known to regulate gene expression in muscle cells and adipocytes. However, transfection of constructs including 2 kb of the GLUT4 promoter fused to the bacterial CAT gene into 3T3-L1 adipocytes displayed only weak promoter activity. Because insulin resistance plays a prominent role in the development of NIDDM, genetic variation in the sequence of GLUT4 also was evaluated. Oligonucleotide primer pairs were selected that allowed the protein-coding region of the human GLUT4 gene to be amplified by PCR. The sequence of the protein-coding region of the GLUT4 gene and all intron-exon junctions was determined for a single diabetic Pima Indian and was identical to that of the cloned gene and cDNA. SSCP analysis was used to screen patients with diabetes mellitus and normal, healthy nondiabetic individuals for mutations at the GLUT4 locus. In addition to the silent substitution in the codon for Asn130 (AAC or AAT) and a Val383 (GTC)-->Ile(ATC) replacement described previously, two new variants were identified. One was a T-->A substitution in intron 1 that was found in 1 of 36 NIDDM patients who were typed for this variant. The second was a Ile385(ATT)-->Thr(ACT) replacement that occurred in 1 normal individual and was not found in any of 676 other normal and diabetic subjects. A large and racially diverse group of normal and diabetic individuals also was screened for the Ile383 polymorphism. It occurred in both diabetic and nondiabetic subjects. There is no indication from our data that these polymorphisms are associated with NIDDM.
Diabetes 1992 Nov
PMID:Human GLUT4/muscle-fat glucose-transporter gene. Characterization and genetic variation. 139 19

NIDDM has a strong genetic component, as evidenced by the high level of concordance between identical twins. The nature of the genetic predisposition has remained largely unknown. Recently, the glucokinase gene locus on chromosome 7p has been shown to be linked to a subtype of NIDDM known as MODY in French and British pedigrees, and glucokinase mutations have been identified. To study the relationship between the glucokinase gene and NIDDM, we performed a linkage analysis in 12 Caucasian pedigrees ascertained through a proband with classical NIDDM. The LINKAGE program was used under four models, including autosomal dominant and recessive, with individuals with glucose intolerance counted as either affected or of unknown status. Linkage was significantly rejected with the dominant models (LOD scores -4.65, -4.25), and was unlikely with the recessive model when glucose intolerance was considered as affected (LOD score -1.38). These findings suggest that mutations in or near the glucokinase gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but do not exclude a role for this locus with a polygenic model, or a major role in some pedigrees.
Diabetes 1992 Nov
PMID:Linkage analysis of glucokinase gene with NIDDM in Caucasian pedigrees. 139 24

The epidemiology of diabetes mellitus in Thai children aged 0-15 years was studied in 1985 and compared with a previous study done in 1984. Four hundred and seventy-six questionnaires were sent each year to hospitals in Thailand. In 1984, thirty-six cases of newly diagnosed diabetes mellitus were found of which 35 were IDDM and one was NIDDM. In 1985, twenty-seven cases of new IDDM were found, no case of NIDDM was reported. Two cases of MRD were reported from the Northeastern and Southern part of Thailand. The incidence of IDDM in the whole kingdom of Thailand was 0.19/100,000/year in 1984 and 0.14/100,000/year in 1985. The male to female ratio was 1:1.5 in 1984 and 1:2 in 1985. The peak age at diagnosis showed the main peak at 14 years old in boys. The peak age of girls preceded boys by 1-2 years in 1984 and 1985. Similar findings in 1984 and 1985 were the onset of symptoms showing a seasonal variation with highest frequency in winter with a slight change of increased incidence in the rainy season of 1985. There was an increased incidence of IDDM in families with lower educational and socioeconomic levels. The newly diagnosed IDDM with DKA was 16.2, and 19.5 per cent in 1984 and 1985. The incidence of IDDM in Thai children, aged 0-15 years seems to be the lowest compared to other countries previously described which might be due to some genetic and environmental including diet, micronutrient, eating habits and life-style which might play a role in the difference.
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PMID:The epidemiology of insulin-dependent diabetes mellitus (IDDM): report from Thailand. 140 45

The effect of race on differences in metabolic control was examined in patients with non-insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetes mellitus. Data were collected on HbA1c, age, duration of diabetes, age at onset, family function, stress, body mass index, waist/hip ratio, total cholesterol, insulin dose, diet, and physical activity. Among those with NIDDM, black patients had significantly higher HbA1c levels than their white counterparts. This difference persisted after adjustment for covariates. Among patients with IDDM, black subjects were found to have higher HbA1c levels, body mass index, and total cholesterol levels than their white counterparts. After correction for diabetes duration, relative insulin dose, physical activity, body mass index, and cholesterol, black women had significantly higher HbA1c levels than black men, white men, or white women. We conclude that race and sex differences do affect the metabolic control of patients with diabetes mellitus.
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PMID:Race-related differences in metabolic control among adults with diabetes. 141 33


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