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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and beta-cell dysfunction. This review focuses on the beta-cell, what defects occur when and why. Two major anatomic observations have been made in NIDDM. The beta-cell mass is mildly reduced, especially when obesity is taken into account. Also, amyloid deposits are frequently observed in the islets. It is unclear whether these changes are genetically mediated or result secondary to the loss of glucose homeostasis. Many studies have looked at some aspect of insulin secretion in NIDDM, and two types of distinct abnormalities have been described. Early on, there is a marked disruption in pulsatile insulin delivery, which is potentially an important contributor to the insulin resistance. It is unclear whether the loss of pulsatile delivery is acquired or genetically induced. Later, after glucose intolerance has started, several other secretory abnormalities develop coincident with loss of beta-cell glucorecognition. The net result is further deterioration in timing of insulin delivery and postprandial hyperglycemia. A second important consequence of the glucose blindness is that the inherent compensatory beta-cell mechanisms that guard against hyperglycemia are bypassed. We propose that the loss of glucose responsiveness is a direct result of an elevated glucose concentration (so-called glucotoxicity) and have generated substantial data in rat models that support this idea. The logical conclusion is that beta-cell function in NIDDM can be maximized by achieving the best metabolic control possible.
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PMID:Natural history of beta-cell dysfunction in NIDDM. 222 13

Although minimal model analysis of frequently sampled iv glucose tolerance tests (FSIGTs) to measure insulin sensitivity is well recognized, application has been limited by the need for endogenous insulin secretion. In the present study we determined whether use of exogenous insulin could permit minimal model assessment of insulin sensitivity (SI) to be extended to diabetic subjects. Normal volunteers had separate FSIGT assessments supplemented with both tolbutamide and insulin to accelerate glucose disappearance, while diabetics had a FSIGT supplemented only with insulin. There was a strong and highly significant correlation between the two assessments in normal subjects (r = 0.87; P less than 0.001), and the rank order of SI generally was maintained with the two assessments over a 3-fold range of SI; however, insulin-determined SI was 16% lower (3.4 +/- 0.4 vs. 4.1 +/- 0.4 x 10(-4) min/microU.microL; P less than 0.01). Diabetic subjects had markedly lower insulin sensitivity than controls (SI = 0.61 +/- 0.16; P less than 0.0001). Across all subjects, the level of fasting serum glucose was correlated inversely with both insulin sensitivity (r = -0.62; P less than 0.05) and acute insulin responses (r = -0.72; P less than 0.02); however, insulin sensitivity in diabetic subjects with little insulin secretion (0.6 +/- 0.2) was comparable to insulin sensitivity in diabetic subjects with near-normal responses (0.6 +/- 0.3). In subjects with fasting hyperglycemia, there were significant correlations between insulin sensitivity and body mass index, percent fat mass, and waist/hip ratio (all P less than 0.03). Among all female subjects, there was also a strong correlation between insulin sensitivity and upper body obesity, as measured by waist/hip ratio (r = -0.68; P less than 0.02). Model parameters also permitted glucose uptake to be estimated in diabetic vs. normal subjects at comparable hyperglycemia (11.1 mmol/L). Total glucose uptake was decreased in diabetic subjects (5.2 +/- 0.8 vs. 12.7 +/- 1.7 mg/min.kg in normals; P less than 0.001), insulin-dependent glucose uptake was diminished to a greater extent (1.3 +/- 0.4 vs. 6.2 +/- 1.2) than noninsulin-independent glucose uptake (3.9 +/- 0.5 vs. 6.4 +/- 0.9; both P less than 0.02). Administration of insulin permits minimal model FSIGT analysis to be applied to diabetic as well as normal subjects, yielding information about both insulin- and noninsulin-mediated glucose uptake as well as insulin sensitivity and insulin secretion.
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PMID:Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. 222 9

Two sensitive and accurate methods for the determination of apo B using polyclonal antibody for human purified LDL are reported. Modified one step EIA by sandwich method is highly sensitive and serum has to be diluted by 1,000-3,000 times, but suited for the diagnosis of hypo or abetalipoproteinemia, detailed analyses of lipoprotein subfractions and in vitro study of lipoprotein metabolism. Latex method is moderately sensitive (serum dilution: 100 times), automated, simple and accurate with CV, 1.5-2.5%. Serum apo B assay is useful not only for the diagnosis of hyperlipidemia, hypolipidemia, but also for the analyses of atherogenic lipoproteins which are frequently associated with large vessel atherosclerotic changes in diabetes, obesity and coronary, cerebral or peripheral vascular diseases. A family pedigree of elevated apo B with frequent association of diabetes (type 2 b) and prominent hypercholesterolemia with autoimmune apo B antibody has been described. In obesity, either hyperinsulinemia or hyperglycemia plays a role in the elevation of VLDL and IDL probably through hepatic overproduction of VLDL. The size of VLDL tends to be larger in VLDL while IDL and LDL seem to become smaller judging from relative lipid contents to apo B.
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PMID:[Highly sensitive apo B assay and its clinical significance]. 223 45

In 102 patients with ischemic heart disease the severity of stenosis was classified into 7 grades (0, 25, 50, 75, 90, 99, 100%) in accordance with the AHA reporting system. The coronary angiograms were compared at first and second catheterization (intervals 2-84 months) and progression was considered present if the stenosis in the second study showed more than one grade increase in comparison with the first study. Fifty six patients met criteria for progression. Risk factors were obtained within the first second catheterization. Drug and diet therapy were evaluated by interview. No significant difference could be found between the progression (P) group and the nonprogression (N) group in relation to family history and obesity. A history of hypertension was more common in the P group. In respect to blood sampling, the values of total cholesterol, Apo B, CII, E and Apo B/AI were significantly higher in the P group than those in the N group at first and second catheterization. The percentage of patients showing abnormal levels of blood sugar and lipid were higher in the P group than the N group although the percentage of patients with drug and diet therapy were higher in the P group than in the N group. The percentage of patients with diet therapy for hyperglycemia and hyperlipidemia were higher in the P group, however weight increase was more common in the P group. These data suggest that sufficient diet and drug therapy is necessary for patients with risk factors.
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PMID:[Prevention of progression of coronary atherosclerosis by drug and diet therapy]. 223 14

To elucidate the nature of lipid defects in patients with diabetes mellitus (DM) concurrent with acute myocardial infarction (MI), the study was undertaken to examine the serum concentrations of total cholesterol, triglycerides, alpha- and beta-lipoproteins with DM in the presence of acute MI. 40 non-diabetic patients with acute MI, 23 diabetics with postinfarct cardiosclerosis, and 17 non-insulin-dependent diabetics without signs of coronary atherosclerosis. Urinary epinephrine and norepinephrine excretion was additionally determined in the acute period and 3-4 weeks after therapy. Homogeneous lipid metabolic parameters were found in CHD patients with and without DM and when transient hyperglycemia developed. The patients with acute MI exhibited some increase in lipid consumption to satisfy the energy need for the cardiovascular system, this being true for triglycerides in DM patients. The DM patients who showed low triglyceride levels had more frequently transmural MI and MI complicated with heart failure. Obesity and familial histories of DM and CHD in DM patients with acute MI were ascertained to be accompanied by reduced serum alpha-lipoprotein concentrations.
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PMID:[The nature of changes in lipid metabolism in patients with diabetes mellitus associated with ischemic heart disease]. 227 41

The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms for an atherogenic action of insulin exist, current evidence does not prove cause and effect and does not warrant withholding insulin therapy (or compromising on dosage) when it is needed.
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PMID:Insulin use in NIDDM. 227 9

Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."
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PMID:The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. 1503 Sep 72

In the present study we examined mRNA and protein levels for the muscle/adipose tissue glucose transporter (GLUT-4) in various tissues of spontaneously obese mice (C57BL/KsJ, db/db) and their lean littermates (db/+). Obese (db/db) mice were studied at 5 wk of age, when they were rapidly gaining weight and were severely insulin resistant, evidenced by hyperglycemia (plasma glucose 683 +/- 60 vs. 169 +/- 4 mg/dl in db/+, P less than 0.05) and hyperinsulinemia (plasma insulin 14.9 +/- 0.53 vs. 1.52 +/- 0.08 ng/ml in db/+, P less than 0.05). The GLUT-4 mRNA was reduced in quadriceps muscle (67.5 +/- 8.5%, P = 0.02), but unaltered in adipose tissue (120 +/- 19%, NS), heart (95.7 +/- 6.1%, NS), or diaphragm (75.2 +/- 12.1%, NS) in obese (db/db) mice relative to levels in lean littermates. The GLUT-4 protein, measured by quantitative immunoblot analysis using two different GLUT-4 specific antibodies, was not different in five insulin-sensitive tissues including diaphragm, heart, red and white quadriceps muscle, and adipose tissue of obese (db/db) mice compared with tissue levels in lean littermates; these findings were consistent when measured relative to tissue DNA levels as an index of cell number. These data suggest that the marked defect in glucose utilization previously described in skeletal muscle of these young obese mice is not due to a decrease in the level of the major muscle glucose transporter. An alternate step in insulin-dependent activation of the glucose transport process is probably involved.
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PMID:Glucose transporter levels in spontaneously obese (db/db) insulin-resistant mice. 231 36

The diabetes-associated changes in regional brain norepinephrine (NE) concentrations and related adrenergic receptor types were correlated with changes in blood glucose levels and body weight (obesity) in 4-16-week-old C57BL/KsJ (db/db) mice relative to corresponding age-matched control (+/?) parameters. Regional brain (i.e. frontal cortex, septal area, amygdala, hypothalamus and medulla) NE levels were determined by high performance liquid chromatography and compared to the associated changes in tissue alpha-1,2 and beta-adrenergic membrane receptor populations. All db/db mice exhibited overt hyperglycemia and obesity relative to controls between 4 and 16 weeks of age. Regional brain NE levels in diabetics were chronically elevated as compared to those of age-matched controls. All of the alpha 1 and alpha 2 adrenergic receptor populations were elevated in the regional brain samples of diabetics relative to controls. In contrast, beta-adrenergic receptor populations were depressed in diabetics as compared with age-matched controls. These data demonstrate that a marked modification in regional brain adrenergic parameters occurs in association with the overt expression of the diabetes mutation in this species. The observed changes in adrenergic influences in specific CNS loci may be causally related to the recognized diabetes-associated alterations in regional brain structure, function and metabolism in C57BL/KsJ (db/db) mice.
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PMID:Age- and diabetes-associated alterations in regional brain norepinephrine concentrations and adrenergic receptor populations in C57BL/KsJ mice. 232 25

Although type II diabetes is associated with both microvascular and macrovascular complications, duration of diabetes and severity of glycemia are strongly associated only with the former. Since prediabetic individuals are hyperinsulinemia, and since hyperinsulinemia may be a cardiovascular risk factor, we hypothesized that prediabetic individuals might have an atherogenic pattern of risk factors even before the onset of clinical diabetes, thereby explaining the relative lack of an association of macrovascular complications with either glycemic severity or disease duration. We documented the cardiovascular risk factor status of 614 initially nondiabetic Mexican Americans who later participated in an 8-year follow-up of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Individuals who were nondiabetic at the time of baseline examination, but who subsequently developed type II diabetes (ie, confirmed prediabetic subjects, n = 43), had higher levels of total and low-density lipoprotein cholesterol, triglyceride, fasting glucose and insulin, 2-hour glucose, body mass index, and blood pressure, and lower levels of high-density lipoprotein cholesterol than subjects who remained nondiabetic (n = 571). Most of these differences persisted after adjustment for obesity and/or level of glycemia, but were abolished after adjustment for fasting insulin concentration. When subjects with impaired glucose tolerance at baseline (n = 106) were eliminated, the more atherogenic pattern of cardiovascular risk factors was still evident (and statistically significant) among initially normoglycemic prediabetic subjects. These results indicate that prediabetic subjects have an atherogenic pattern of risk factors (possibly caused by obesity, hyperglycemia, and especially hyperinsulinemia), which may be present for many years and may contribute to the risk of macrovascular disease as much as the duration of clinical diabetes itself.
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PMID:Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? 233 55


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