bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Glucose-Transporter Gene Expression In Vitro and In Vivo
Authors: Kahn Barbara B , Flier Jeffrey S
Published: March 2007

Understanding of the fundamental mechanisms underlying the complex regulation of glucose homeostasis has been dramatically transformed recently by the realization that glucose transport in mammalian tissues is mediated by a family of structurally related but genetically distinct glucose-transporter proteins. The regulatory factors and intracellular signaling pathways that influence expression of the genes encoding these proteins are just being identified. Factors that regulate glucose-transporter gene expression in vitro include oncogenes, growth factors, insulin, oral hypoglycemic agents, vanadate, glucocorticoids, ambient glucose levels, and the state of cellular differentiation. In vivo, glucose-transporter gene expression in adipose cells, skeletal muscle, and liver is markedly affected by various altered nutritional and metabolic states. Recent studies have demonstrated that two glucose transporters expressed in the same tissue may be regulated differently in response to the same metabolic perturbation. Furthermore, transporter regulation appears to be tissue specific. These observations lay the groundwork for future studies aimed at unraveling the functional roles of the individual transporter species in different tissues, the molecular processes involved in regulating the expression of these genes, and the impact of dysregulated glucose-transporter gene expression in the pathogenesis of insulin-resistant states such as diabetes.
Glucose Toxicity
Authors: Rossetti Lciano , Giaccari Andrea , DeFronzo Ralph A
Published: March 2007

Glucose toxicity is a well-established entity that has been shown in animal models of diabetes to contribute to development of insulin resistance and impaired insulin secretion. In type II (non-insulin-dependent) diabetes in humans, a considerable body of evidence has accumulated indicating that a chronic physiological increment in the plasma glucose concentration leads to progressive impairment in insulin secretion and may contribute to insulin resistance as well. The precise biochemical mechanism(s) responsible for the hyperglycemia-induced defect in insulin secretion remains to be defined but may be related to a defect in phosphoinositide metabolism. In animal models of diabetes, development of insulin resistance is related to downregulation of the glucose-transport system, and a similar phenomenon is also likely to occur in humans. In addition, hyperglycemia in humans may lead to a defect in glycogen synthesis. In this respect, humans may be different from rats. In type I (insulin-dependent) diabetic patients who are poorly controlled, insulin resistance is a characteristic feature and can be ameliorated by tight glycemic control, suggesting that hyperglycemia is responsible for the insulin resistance. Evidence also has accumulated to implicate glucose toxicity in the functional impairment in insulin secretion that occurs during the initial presentation of patients with type I diabetes, and this may explain the honeymoon period so commonly observed after the institution of insulin therapy.
Role of Insulin in Management of Surgical Patients With Diabetes Mellitus
Authors: Hirsch Irl B , McGill Janet B
Published: March 2007

Because surgery is a likely event during the lifetime of patients with diabetes, health-care team members need to be aware of the metabolic problems that may occur during the perioperative period. Surgery, especially in the presence of general anesthesia, will produce a diabetogenic response. This is generally due to an elevation of counterregulatory hormones, although endogenous insulin is also suppressed. The excessive lipolysis and ketogenesis that can occur during surgery can have particularly deleterious effects for patients with diabetes. Thus, sufficient insulin must be provided during this period to suppress these catabolic processes. The major controversy regarding surgery and diabetes concerns the route of insulin administration. This article reviews the various treatment options for patients with insulin-dependent and non-insulin-dependent diabetes mellitus, with particular emphasis on the role of insulin. Special situations, e.g., outpatient surgery, coronary artery bypass, and emergency surgery, are also discussed.
Antihypertensive Therapy With Ca2+: Antagonist Verapamil and/or ACE Inhibitor Enalapril in NIDDM Patients
Authors: Ferrier Claudia , Ferrari Paolo , Weidmann Peter , Keller Ulrich , Beretta-Piccoli Carlo , Riesen Walter F
Published: March 2007

Objective

To assess the efficacy and tolerance of a diuretic-free antihypertensive therapy with a Ca2+ antagonist and an angiotensin-converting enzyme (ACE) inhibitor in patients with non-insulin-dependent diabetes mellitus (NIDDM).

Research Design and Methods

After a 2-wk washout and a 4-wk placebo phase, 47 hypertensive patients with NIDDM randomly received verapamil or enalapril alone and, if blood pressure remained elevated, both agents combined over 30 wk.

Results

Verapamil or enalapril alone normalized blood pressure to < 90 mmHg diastolic in 30 patients; verapamil decreased mean ± SE blood pressure from 159/98 ± 3/1 to 146/87 ± 3/2 mmHg (n = 18, P < 0.001) and enalapril from 166/99 ± 5/2 to 146/86 ± 3/1 mmHg (n = 12, P < 0.001). In 17 patients who were still hypertensive after 10 wk of monotherapy, combination of both drugs decreased blood pressure from 170/104 ± 4/2 to 152/90 ± 4/2 mmHg (P < 0.001). Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total lipids, high-density and low-density lipoprotein cholesterol, apolipoproteins A-I and B, creatinine, and urinary albumin-creatinine ratio were not significantly modified.

Conclusions

In hypertensive patients with NIDDM, a diuretic-free therapy based on the Ca2+ antagonist verapamil and/or the ACE inhibitor enalapril can effectively decrease blood pressure without adversely affecting carbohydrate and lipid metabolism.
Dyslipidemia in type II Diabetes: Implications for Therapeutic Intervention
Authors: Stern Michael P , Haffner Steven M
Published: March 2007

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.
Endothelium and Regulation of Coagulation
Authors: Stern David M , Esposito Ciro , Gerlach Herwig , Gerlach Marlene , Ryan Jane , Handley Dean , Nawroth Peter
Published: March 2007

Endothelial cells form the luminal vascular surface and thus have a central role in the regulation of coagulation. One important way in which endothelial cells control the clotting system is by regulating the expression of binding sites for anticoagulant and procoagulant factors on the cell surface. In the quiescent state, endothelial cells maintain blood fluidity by promoting the activity of numerous anticoagulant pathways, including the protein C/protein S pathway. After activation, as can be brought about by cytokines, the balance of endothelial properties can be tipped to favor clot formation through coordinated induction of procoagulant and suppression of anticoagulant mechanisms. Tumor necrosis factor suppresses the endothelial anticoagulant cofactor thrombomodulin and induces expression of the procoagulant cofactor tissue factor. Working in concert, these changes can allow fibrin formation to proceed in an inflamed focus but maintain blood fluidity in the surrounding area of normal vasculature. Recent studies suggest that similar changes in endothelial coagulant properties can be induced by advanced glycosylation end products, proteins modified by glucose that accumulate in the vasculature at a rapid rate in diabetic subjects, indicating the potential relevance of these mechanisms in diabetic vascular disease.
Effects of Adrenergic Blockade on Serum Potassium Changes in Response to Acute Insulin-Induced Hypoglycemia in Nondiabetic Humans
Authors: Fisher B Miles , Thomson Ian , Hepburn David A , Frier Brian M
Published: March 2007

Objective

To determine the possible role of adrenergic mechanisms in mediating the fall in serum potassium concentration after intravenous injection of insulin.

Research Design and Methods

Eighteen nondiabetic male volunteers, divided into three groups of six subjects, comprised the study. Hypoglycemia was induced by a bolus of short-acting insulin (0.15 U∕kg body wt). Six subjects were studied in control conditions, six during α-adrenergic blockade with phentolamine, and six during β-adrenergic blockade with propranolol.

Results

In the control group, there was an immediate fall in serum potassium from 4.0 ± 0.1 to 3.6 ± 0.1 mM at baseline + 15 min. After the onset of acute hypoglycemia, potassium decreased further in the control group, reaching a lowest concentration of 3.3 ± 0.1 mM. In the propranolol group, the late decrease in potassium was inhibited, and there were no further changes in serum potassium. During α-blockade, there was an exaggerated fall to 2.6 ± 0.1 mM at 30 min after the onset of hypoglycemia.

Conclusions

The later fall in serum potassium, which occurs after the onset of hypoglycemia, is probably mediated by stimulation of β-adrenoreceptors, whereas coincidental stimulation of α-adrenoreceptors opposes this fall in potassium and may prevent the development of severe hypokalemia in response to acute hypoglycemia.
Comparison of Subcutaneous Soluble Human Insulin and Insulin Analogues (AspB9, GluB27; AspB10; AspB28) on Meal-Related Plasma Glucose Excursions in Type I Diabetic Subjects
Authors: Kang Steven , Creagh Fionuala M , Peters John R , Brange Jens , Vølund Aage , Owens David R
Published: March 2007

Objective

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100).

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100).

Research Design and Methods

Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (∼ 12 U)s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal.

Results

Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 ± 0.8 mM), mean ± SE peak incremental glucose rises were similar after analogues AspB10 (5.4 ± 0.8 mM) and AspB9, GluB27 (5.4 ± 0.7 mM) and significantly lower after analogue AspB28 (3.6 ± 1.2 mM, P < 0.02). Relative to soluble human insulin (100% ± SE21), incremental areas under the glucose curve between 0 and 240 min were 79% ± 34 (AspB10, NS), 70% ± 29 (AspB9, GluB27, NS), and 43% ± 23 (AspB28, P < 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 ± 44 pM (AspB10); 1231 ± 190 pM (AspB9, GluB27) and 414 ± 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 ± 15 pM (P < 0.02 in each case).

Conclusions

Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.
Costs of Temporary and Permanent Disability Induced by Diabetes
Authors: Olivera Ercilia M , Duhalde Esteban Péerez , Gagliardino Juan Jose
Published: March 2007

Objective

To evaluate the indirect costs of diabetes and show their relationship to the chronic complications of diabetes.

Research Design and Methods

The cost of temporary and permanent disability for diabetic patients was studied in a group of La Plata University employees and in a second group at the government institutions of the Buenos Aires Province during 3 consecutive yr (1984–1986).

Results

Absences due to temporary disability were similar for the diabetic group without chronic complications and an age-and sex-matched nondiabetic control group. Conversely, diabetic patients with chronic complications had major increases in absences compared with the control subjects. Diabetes mellitus was the third leading cause of permanent disability mainly due to macrovascular and retinal lesions. This disability resulted in an average of 11 yr of work production loss per patient.

Conclusions

These results suggest that diabetic individuals without complications incur few additional costs compared with nondiabetic individuals. However, once complications appear, the indirect costs are very high, suggesting that secondary preventions of the diabetic complications might be an optimal approach for reducing the health-care burden of diabetes.
Retrospective Analysis of Posttransplantation Diabetes Mellitus in Black Renal Allograft Recipients
Authors: Sumrani Nabil B , Delaney Vera , Daskalakis Paula , Davis Robert , Friedman Eli A , Hong Joon H , Sommer Bruce G
Published: March 2007

Objective

To study the incidence, outcome, and possible etiopathogenic factors involved in posttransplantation diabetes mellitus in cyclosporine-treated black renal allograft recipients.

Research Design and Methods

One hundred thirty-eight nondiabetic black renal transplant recipients whose grafts survived > 1 yr were studied retrospectively.

Results

Twenty-eight (20.3%) patients developed posttransplantation diabetes mellitus, 46 and 75% were diagnosed by 6- and 12-mo posttransplantation, respectively, and 46% were insulin dependent. Diabetes was more frequently encountered in older recipients and recipients of cadaveric kidneys but was independent of sex, number of transplants, incidence of acute rejection, percentage of body weight gain, steroid or cyclosporine dose, and use of beta-blockers and/or diuretics. Renal function was similar in the diabetic group compared with the control group. Actuarial 5-yr graft survival was 82% in the diabetic cohort compared with 78% in the control group, with chronic rejection accounting for all graft losses within the diabetic group.

Conclusions

Twenty percent of black cyclosporine-treated renal allograft recipients developed diabetes mellitus in the posttransplantation period. However, its presence did not appear to influence intermediate-term graft or patient survival.
Low-Protein Diets in Renal Disease
Authors: Zeller Kathleen R
Published: March 2007

End-stage renal disease is a major cause of morbidity and mortality in the U.S. population and a significant contributor to national health-care expenditures. In recent years, a growing body of literature has accumulated from studies in animals and humans to suggest that dietary protein restriction can significantly retard the progression of chronic renal insufficiency. This article reviews the relevant literature and outlines the questions that remain for future investigation.
Dyslipidemias Among Normoglycemic Members of Familial NIDDM Pedigrees
Authors: Schumacher Mary Catherine , Maxwell Teresa M , Wu Lily L , Hunt Steven C , Williams Roger R , Elbein Steven C
Published: March 2007

OBJECTIVE

To examine the hypothesis that hyperinsulinemia among relatives of NIDDM probands will increase the prevalence of DLPs, we measured insulin levels and examined the frequency of DLPs among NIDDM pedigree members.

RESEARCH DESIGN AND METHODS

We performed 2-h 75-g OGTTs and measured lipid and insulin levels of 287 family members and 86 spouses from 16 large Utah pedigrees ascertained for ≥ 2 siblings with NIDDM.

RESULTS

One-hour insulin levels were higher among 206 family members with NGT than among 65 NGT spouses (483.3 vs. 361.7 pM, P = 0.05). Among the NGT family members, 32% had cholesterol levels at or above the age- and sex-specific 90th percentile level defined by the LRC studies, 33% had HDL levels ≤ 10th percentile, and 20% had triglyceride levels ≥ 90th percentile. DLP (any of the three abnormalities) was found among 58% of NGT family members, which was significantly higher than the expected 27% (P < 0.00001) and the prevalence among spouses of 45% (P < 0.05). By NCEP criteria for hyperlipidemia, 40% of family members met criteria for diet and/or pharmacological therapy.

CONCLUSIONS

Normoglycemic members of NIDDM pedigrees have a high prevalence of DLPs, which approaches the prevalence in patients with NIDDM. Our data suggest that members of NIDDM pedigrees should be screened carefully for lipid abnormalities.
Quality of Life of Pancreatic Transplant Recipients
Authors: Milde Frances K , Hart Laura K , Zehr Pamela S
Published: March 2007

OBJECTIVE

To comprehensively assess and compare pancreas/kidney transplant recipients' quality of life.

RESEARCH DESIGN AND METHODS

This quasi-experimental comparative study of 31 successful and 13 failed pancreas transplant recipients collected data from persons who had received pancreas and kidney transplants ≥6 mo prior at a university tertiary care center. Physical and social function, symptoms, mental state, and sense of well-being of the recipients were assessed.

RESULTS

Groups did not differ significantly regarding age, gender, marital status, onset or length of diabetes, comorbidity, type of prior dialysis, current kidney function, length of time since transplant, physical activity, symptom burden, emotional state, feelings of well-being, and present quality of life and health. A significant time by group interaction occurred for quality of life (P = 0.0013) and health (P = 0.0001). The successful group indicated that both quality of life and health were significantly better than in the past, and continued improvement was expected. The unsuccessful group did not have this perception. Members of the failed group were significantly more satisfied with their social support. The unsuccessful group's major concerns related to diabetes, not immunosuppression.

CONCLUSIONS

Recipients of successful pancreas transplants perceived their improvement in health and quality of life to be significantly greater than the unsuccessful recipients.
Dropout and Relapse During Diabetes Care
Authors: Graber Alan L , Davidson Patricia , Brown Anne W , McRae John R , Woolridge Kathleen
Published: March 2007

OBJECTIVE

To determine factors associated with dropout and relapse during chronic diabetes care.

RESEARCH DESIGN AND METHODS

Private practice outpatient treatment-education program for adult diabetes was surveyed. Retrospective analysis was done, involving 422 patients for up to 3 yr.

RESULTS

Of the patients in the study, 12% dropped out after the initial visit, and 33% of the residual cohort dropped out during each subsequent 6-mo period. Factors associated with dropout included distance from home to clinic > 100 miles, lack of insulin treatment, and cigarette smoking. In patients who remained in follow-up, a significant decrease in HbA1C occurred during the first 6 mo, but 40% of the patients relapsed between 6 and 12 mo. Frequency of relapse declined as time passed. Relapse was more frequent in women.

CONCLUSIONS

Dropout from treatment and relapse after temporary improvement account for a substantial amount of uncontrolled diabetes, and overcoming the obstacles of dropout and relapse has potential for significant improvement in diabetes care.
A Multisite Physician's Office Laboratory Evaluation of an Immunological Method for the Measurement of HbA1c
Authors: Guthrie Richard , Hellman Richard , Kilo Charles , Hiar Charles E , Crowley Lawrence E , Childs Belinda , Fisher Robin , Pinson Mary Beth , Suttner Audrey , Vittori Christine
Published: March 2007

OBJECTIVE

To evaluate the clinical performance of a new immunological HbA1c method in physicians' office laboratories.

RESEARCH DESIGN AND METHODS

Three physicians' offices participated in the evaluations. The clinicians routinely use HbA1c test results to monitor their patients' long-term blood glucose control. Precision and interlaboratory variability were assessed using three levels of lyophilized controls. Correlation of the method's results to currently available laboratory methods was made. Comparison of finger-stick (capillary) results to venous EDTA whole blood results was made on 134 patients. Physician and laboratory personnel input was evaluated with regard to the clinical utility of the system.

RESULTS

The CVW and CVB were a maximum of 4.5 and 4.4% for the immunoassay system on three levels of control materials at the three sites. Interlaboratory variability among the control means was found to be 4.9–5.4, 8.0–8.3, and 11.7–12.0% HbA1c. Correlation coefficients (r) ranged from 0.95 to 0.99. There was a positive bias by the DCA 2000 compared with the in-house method at site 1. Minimal negative biases were seen by the DCA 2000 with comparative methods used at sites 2 and 3. Median percentage differences with the comparative methods were 12, −1.4, and −5.6%. Comparison of capillary to venous sample results, from the DCA 2000, showed no clinically significant differences. Operator and physician feedback were positive with respect to technical ease in performance of the test and accuracy of results.

CONCLUSIONS

Precision was acceptable and interlaboratory variability was low. The immunological method correlated well with manual ion-exchange and automated HPLC methods. The small sample size and good comparison between capillary and venous sample results make fingerstick sampling acceptable. The method provided immediate test results (within 9 min) to the clinicians.
Effect of High Carbohydrate Intake on Hyperglycemia, Islet Function, and Plasma Lipoproteins in NIDDM
Authors: Garg Abhimanyu , Grundy Scott M , Koffler Michael
Published: March 2007

OBJECTIVE

To study effects of high carbohydrate intake on hyperglycemia, islet functions, and plasma lipoproteins in patients with NIDDM.

RESEARCH DESIGN AND METHODS

An attempt was made to induce hyperglycemia in 10 men with NIDDM by feeding them an isocaloric high-carbohydrate diet (65% of energy as simple carbohydrates [31% as glucose] and 20% as fat) for 28 days in a metabolic ward. Response to the high-carbohydrate diet was compared with that of feeding a diet rich in monounsaturated fat (45% of energy as fat [31% as monounsaturated fat] and 38% as carbohydrates) for 28 days in a cross-over manner. Islet functions were assessed by evaluating plasma glucose, insulin, C-peptide and glucagon responses to standard meal tolerance tests on days 0, 14, 21, and 28 of each dietary period. Fasting plasma lipoproteins were determined during the last week of each dietary period.

RESULTS

The high-carbohydrate diet caused significant but modest accentuation of hyperglycemia, particularly in patients with moderately severe diabetes mellitus, whereas no change was observed with the high-monounsaturated fatty-acid diet. Accentuation of hyperglycemia was accompanied by an increase in plasma glucagon levels, but no significant change in insulin and C-peptide responses. In 1 patient, feeding the high-carbohydrate diet for 68 days produced marked hyperglycemia and caused definite suppression of insulin and C-peptide responses along with an increase in glucagon levels. Compared with the high-monounsaturated fat diet, the high-carbohydrate diet also raised plasma triglyceride and VLDL cholesterol concentrations.

CONCLUSIONS

High-carbohydrate diets may cause accentuation of hyperglycemia and a rise in plasma glucagon levels in NIDDM patients. High-carbohydrate diets also adversely affect lipoproteins and therefore may not be desirable in all NIDDM patients.
Insulin-Receptor Activity in Nondiabetic and Diabetic Urbanized South African Black Women
Authors: Panz Vanessa R , Joffe Barry I , Wing Jeffrey R , Raal Frederick J , Seftel Harold C
Published: March 2007

Objective

To evaluate insulin receptor binding characteristics of urbanized South African black women with normal glucose tolerance and of patients with newly diagnosed untreated non-insulin-dependent diabetes mellitus (N1DDM).

Research Design and Methods

Four groups of 10 subjects each were selected by the following criteria: group A, young (20-39 yr) nonobese (body mass index [BMI] 19.0-24.9 kg/m2) nondiabetic women; group B, middleaged (40–60 yr) nonobese nondiabetic women; group C, middle-aged obese (BMI>30.0 kg/m2) nondiabetic women; and group D, middle-aged obese newly diagnosed but untreated female patients with NIDDM. Insulin binding to monocyte receptors was determined by radioreceptor assay. Fasting plasma samples were analyzed for glucose, insulin, C-pep tide, and nones terified fatty acids.

Results

In the four groups studied, maximum specific binding and receptor concentration were highest in group A, with a progressive and significant decrease in values through groups B and C to group D. Significant inverse correlations were obtained between maximum specific binding, 50% inhibition dose, and total receptor concentration on the one hand and glucose, insulin, and NEFA on the other.

Conclusions

Our study of urban South African black women showed decreasing insulin-receptor activity with obesity and glucose intolerance. In patients with NIDDM, hyperglycemia and (β-cell dysfunction were associated with a reduction in receptor concentration. In this regard, our findings in South African blacks are consistent with results of similar studies of NIDDM in other communities.
Pittsburgh Epidemiology of Diabetes Complications Study: Measuring Diabetic Neuropathy Follow-up Study Results
Authors: Maser Raelene E , Becker Dorothy J , Drash Allan L , Ellis Demetrius , Kuller Lewis H , Greene Douglas A , Orchard Trevor J
Published: March 2007

Objective

This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospective study.

Research Design and Methods

Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing, nerve conduction studies, and clinical examination.

Results

Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam ∼2 yr later, the sensitivity for vibratory thresholds was high (100%). Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline.

Conclusion

Despite a cross-sectional relationship between the assessment modalities and clinically overt neuropathy at baseline, these follow-up data suggest that the potential for the objective modalities as predictors of clinically diagnosed neuropathy may be limited.
Sex Differences in Secondary Attack Rate of IDDM to Siblings of Probands Through Older Ages: Pittsburgh Etiology of IDDM Study
Authors: Gavard Jeffrey A , Dorman Janics S , LaPorte Ronald E , Orchard Trevor J , Drash Allan L , Trucco Massimo M , Kelsey Sheryl F , Kostraba Jill N , Becker Dorothy J
Published: March 2007

Objectives

To determine the descriptive epidemiological patterns of the secondary attack rate of insulin-dependent diabetes mellitus (IDDM) among siblings of probands through older ages.

Research Design and Methods

A family history analysis was performed on 1774 IDDM probands who were diagnosed or seen within 1 yr of diagnosis at Children's Hospital of Pittsburgh from 1 January 1950 through 31 December 1981. The probands were discharged on insulin and were diagnosed at <17 yr of age. The time frame permitted the risk of IDDM for siblings of probands to be calculated over a broad spectrum of age.

Results

Risk estimates for the 3966 full natural siblings through 10, 20, and 30 yr of age were 1.6, 4.1, and 6.3%, respectively. Secondary attack rates were equivalent for male and female siblings through 15 yr of age (3%); however, the risk to males increased an additional 4% between 16 and 30 yr of age compared with 2.5% for females (P = 0.01). There was no evidence of an excess sex concordance among affected sibling pairs.

Conclusions

Males have a greater secondary attack rate of IDDM at older ages than females. This may be due to an increased exposure to environmental agents among males or protective influences operating among females.
Diabetic Nephropathy: Future avenue
Authors: Viberti GianCarlo , Yip-Messent Jeannie , Morocutti Anna
Published: March 2007

Diabetes mellitus has become the leading cause of ESRF in the United States. Patients with diabetic nephropathy suffer high cardiovascular morbidity and mortality. Because only 40% of diabetic patients eventually develop diabetic kidney disease, it may be possible to devise primary prevention measures targeted at the subset of patients at risk. Recently, a predisposition to hypertension, a family history of diabetic nephropathy, and a family history of CVD disease each have been associated independently with the development of diabetic renal complication in IDDM. Risk factors for macrovascular damage, including raised arterial BP, dyslipidemia, and insulin resistance, can be detected early in the course of progression to diabetic nephropathy. These risk indicators recently have been shown to be already present at the stage of normoalbuminuria in those patients who eventually will progress to microalbuminuria. Treatment of established renal disease can only delay the onset of ESRF, and lowering of microalbuminuria has been shown to retard the onset of persistent proteinuria. However, no study to date has demonstrated prevention of renal disease in these patients. The ultimate aim should, therefore, be the prevention of the transition from normoalbuminuria to microalbuminuria in individuals who are at higher risk of diabetic renal disease and CVD.
Coronary Heart Disease Risk Factors in Morbidly Obese Women With Normal Glucose Tolerance
Authors: Barakat Hisham A , Mooney Nitin , O'Brien Kevin , Long Stuart , Khazani Prabhaker G , Pories Walter , Caro Jose F
Published: March 2007

Objective— To examine if the risk for CHD increases progressively with increases in the BMI of normoglycemic, hyperinsulinemic, morbidly obese women (BMI ≥ 35 kg/m2).

Research Design and Methods— Insulin sensitivity was evaluated by calculating an ISI following an OGTT. There was a significant linear relationship between ISI and BMI fitted by two straight lines intersecting at a point corresponding to a BMI of 29.7 ± 1.5 kg/m2. Significant linear relationships between insulin sensitivity and BMI were obtained below and above this breakpoint. Similarly, a breakpoint for the relation between dBP and BMI corresponding to a BMI ≥ 33.7 ± 3.4 kg/m2 was obtained. Significant linear relationships between BMI and plasma fasting glucose, triglyceride, cholesterol, HDL cholesterol, sBP, or dBP were not observed in the women with a BMI > 35 kg/m2.

Results— Compared with lean (BMI <27) women of similar age, the morbidly obese patients appear to be at a higher risk for CHD. This is suggested by statistically significant increases in fasting insulin (mean ± SD; 187 ± 137 vs. 64.2 ± 16.2 pM) and triglyceride levels (128 ± 78.1 vs. 73 ± 25 mg/dl), sBP (132 ± 114 vs. 104 ± 15.8) and dBP (84 ± 72 vs. 67 ± 2.1 mmHg), and decreases in HDL cholesterol (1.03 ± 0.44 vs. 1.29 ± 0.82 mM) and apo A-I (91 ± 55 vs. 122 ± 35 mg/dl) concentrations.

Conclusions— It appears that there may be a threshold of body mass up to which insulin sensitivity is associated with CHD risk. Above this threshold, there does not appear to be a progressive increase in the risk factors for CHD with increases in BMI.
Clinical Hypertension and Its Interaction With Diabetes Among American Indians and Alaska Natives: Estimated rates from ambulatory care data
Authors: Broussard Brenda A , Valway Sarah E , Kaufman Stephen , Beaver Shelli , Gohdes Dorothy
Published: March 2007

OBJECTIVE— To estimate the prevalence of clinical hypertension and describe the coexistence with diabetes in American Indian and Alaska Native communities.

RESEARCH DESIGN AND METHODS— A cross-sectional study of outpatient visits for hypertension and diabetes over a 1-yr period (1 October 1986 to 30 September 1987) in IHS facilities was conducted.

RESULTS— The 1987 estimated age-adjusted prevalence of diagnosed hypertension for this group was 10.9/100 for people ≥15 yr of age. Thirty-seven percent of diabetic patients were diagnosed with hypertension. The relative risk of hypertension in the diabetic populations compared with the nondiabetic population varied from 4.7 to 7.7 among the different IHS areas.

CONCLUSIONS— Despite high rates of diabetes and obesity, hypertension rates were relatively low among American Indians and Alaska Natives when compared with other ethnic groups in the U.S.
Diabetes and Obesity in the Offspring of Pima Indian Women With Diabetes During Pregnancy
Authors: Pettitt David J , Nelson Robert G , Saad Mohammed F , Bennett Peter H , Knowler William C
Published: March 2007

OBJECTIVE— To review the long-term effects of the diabetic pregnancy on the offspring among the Pima Indians of Arizona.

RESEARCH DESIGN AND METHODS— Studies published by the Phoenix Epidemiology and Clinical Research branch of the National Institute of Diabetes and Digestive and Kidney Diseases, since the inception of the longitudinal diabetes studies in 1965 were reviewed. In addition, pertinent studies from other centers, mentioned as references in these publications, were reviewed. As far as possible, all original articles and abstracts on this aspect of the Pima Indian studies were discussed.

RESULTS— The offspring of women who had diabetes during pregnancy, on average, were more obese and had higher glucose concentrations and more diabetes than the offspring of women who developed diabetes after pregnancy or who remained nondiabetic. Although no new analyses were attempted, several of the older publications were updated by repeating the analyses on later, expanded data sets.

CONCLUSIONS— The diabetic pregnancy, in addition to its effects on the newborn, has effects on the subsequent growth and glucose metabolism of the offspring. These effects are in addition to genetically determined traits.
Diabetes Mellitus in Tohon O'odham Pregnancies
Authors: Livingston Robert C , Bachman-Carter Karen , Frank Christine , Mason William B
Published: March 2007

OBJECTIVE— To determine the prevalence of diabetes in Tohono O'odham pregnancies, and to assess the efficacy of early prenatal diabetes screening in populations with high rates of diabetes.

RESEARCH DESIGN AND METHODS— All Tohono O'odham women receiving prenatal care at the Sells Service Unit who delivered a viable baby in the 5-yr study period were reviewed.

RESULTS— Diabetes was confirmed in 97 of 1854 (5.2%) Tohono O'odham pregnancies delivered during the study period. NIDDM antedated pregnancy in 38 (39%) of the diabetic pregnancies. Diabetes was diagnosed for the first time in 59 (61%) of these diabetic pregnancies. The diagnosis was made at or before the 20th gestational wk in 25 of 59 (42%) gestational diabetic women. These 25 women represented 61% of 41 gestational diabetic women who received prenatal care at or before the 20th gestational week.

CONCLUSIONS— Our findings indicate that first trimester diabetes screening is justified in this population and may be appropriate in other populations with high rates of diabetes.
Disruptive Effects of Acute Hypoglycemia on Speed of Cognitive and Motor Performance
Authors: Cox Daniel J , Gonder-Frederick Linda A , Schroeder Deborah B , Cryer Philip E , Clarke William L
Published: March 2007

OBJECTIVE

To directly examine whether hypoglycemia differentially slows cognitive versus motor function, to evaluate the reliability of hypoglycemic-related slowing, and to examine factors contributing to individual differences.

RESEARCH DESIGN AND METHODS

IDDM subjects (n = 10) were administered a pure cognitive and a pure motor neuropsychological test at euglycemia (5.4 mmol), blood glucose nadir (2.6 mmol), postnadir (3.6 mmol), and again at euglycemia (6.7 mmol). To assess the practice effect, matched control subjects were tested at similar time intervals.

RESULTS

Concurrent and test-retest reliability for all tests was robust (r = 0.68–0.94). Only cognitive tasks demonstrated impairment at nadir (P < 0.04). Individual differences, in terms of cognitive impairment, were significantly correlated with levels of blood glucose at nadir and baseline performance.

CONCLUSIONS

Cognitive tasks appear to be more sensitive to neuroglycopenia than motor tasks. Cognitive impairment caused by hypoglycemia is reliable and differs across subjects. Individuals who show reliable sensitivity to cognitive impairments of hypoglycemia should avoid moderately low blood glucose levels.
Regional Cerebral Blood Flow and Cerebrovascular Reactivity in IDDM
Authors: Rodriguez Guido , Nobili Fiavio , Celestino Maria Assunta , Francione Stefano , Gulli Giovanni , Hassan Khalil , Marenco Stefano , Rosadini Guido , Cordera Renzo
Published: March 2007

OBJECTIVE

To investigate both rCBF and cerebrovascular reactivity, evaluated as pre- and post-ACZ rCBF differences in a group of IDDM patients with differences in duration of disease and severity of complications.

RESEARCH DESIGN AND METHODS

rCBF was measured by the 133Xenon inhalation method in 20 IDDM patients and in 15 healthy control subjects before and after an intravenous injection of ACZ, a carbonic anhydrase inhibitor commonly used to assess cerebrovascular reactivity.

RESULTS

Basal global CBF (the mean of 32 regional values) was within the normal range in all patients but 1, who showed slight hyperperfusion; moreover, in 3 patients with long-lasting disease, some hypoperfused regions were found. ANOVA showed an inverse correlation between basal global CBF (P < 0.01) and duration of diabetes, but no correlation with Hb, MABP, serum glucose concentration, or GHb. Compared with control subjects, the percentage of global CBF increment after ACZ administration was significantly impaired in 4 patients and gave a borderline response in 2 patients; 4 of these poor ACZ responders had retinopathy, and 1 had suffered from a TIA. Duration of diabetes, Hb, MABP, serum glucose concentration, and GHb did not correlate with the percentage of post-ACZ global CBF changes, and did not differ among the 6 poor ACZ responders and the other diabetic patients or control subjects.

CONCLUSIONS

These results confirm that global CBF is within the normal range in most IDDM patients, although it is significantly influenced by the duration of diabetes; pathophysiological correlates of the altered cerebrovascular reactivity need to be further investigated. rCBF measurements, before and after ACZ administration, seem to represent a safe and reliable tool for assessing cerebrovascular function in IDDM.
Low-Dose Acarbose Improves Glycemic Control in NIDDM Patients Without Changes in Insulin Sensitivity
Authors: Jenney Adam , Proietto Joe , O'Dea Kerin , Nankervis Alison , Traianedes Kathy , D'Embden Helen
Published: March 2007

OBJECTIVE

To examine the impact on metabolic control in NIDDM patients of the alpha-glucosidase inhibitor, acarbose, when administered at a low dose in powdered form.

RESEARCH DESIGN AND METHODS

Six subjects were recruited for a double-blind cross-over trial using 25 mg powdered acarbose and a placebo 3 times a day with meals for 3 mo. In addition to parameters of diabetes control and body weight, glucose turnover and insulin sensitivity were measured with the hyperinsulinemic/euglycemic clamp technique combined with tracer kinetics.

RESULTS

None of the subjects showed significant changes in FPG levels or body weight either on the 3-mo course of acarbose or placebo. HbA1c fell significantly from 10.6 ± 1.0 to 9.4 ± 1.3% (P = 0.05) during treatment with acarbose but failed to change on placebo (10.1 ± 1.0 to 11.1 ± 2.0%; P = 0.36). Basal HGP and glucose utilization were unchanged during either of the treatment periods, and hyperinsulinemia produced a similar degree of suppression of HGP before and after each treatment. At a physiological concentration, insulin failed to stimulate glucose clearance in these diabetic patients, and no improvement was seen with acarbose treatment. No changes in plasma lipids or lipoprotein profiles were demonstrated after 3 mo on acarbose. In acute studies, it was shown that administration of acarbose at a dose of 25 mg powder per meal significantly decreased the postprandial glycemic excursion.

CONCLUSIONS

When administered in the powdered form at the low dose of 25 mg 3 times/day with meals over 3 mo, acarbose was well tolerated by the NIDDM patients and was without side effects. It improved glycemic control by reducing postprandial hyperglycemia, but had no effect on glucose turnover, insulin sensitivity, or lipid profile.
Effect of Aldose Reductase Inhibitor (Tolrestat) on Urinary Albumin Excretion Rate and Glomerular Filtration Rate in IDDM Subjects With Nephropathy
Authors: Passariello N , Sepe J , Marrazzo G , De Cicco A , Peluso A , Plsano MCA , Sgambato S , Tesauro P , D'Onofrio F
Published: March 2007

OBJECTIVE

To explore the possible link between diabetic nephropathy and the enhanced activity of the polyol pathway, known to occur in IDDM subjects.

RESEARCH DESIGN AND METHODS

We studied the effects of the aldose reductase inhibitor tolrestat (200 mg/day) on urinary albumin excretion rate and glomerular filtration rate in 20 IDDM patients with diabetic nephropathy.

RESULTS

Six months of placebo treatment produced no significant changes in glomerular filtration rate, urinary albumin excretion rate, and renal plasma flow. Consequently, filtration fraction remained unchanged. During tolrestat treatment, glomerular filtration rate decreased from the basal value of 156 ± 14 ml·min−1.73 m2 to 142 ± 13.7 ml·min−1·1.73 m2 (P < 0.001) at 2 mo; 128 ± 12.4 ml·min−1·1.73 m2 (P < 0.001) at 4 mo; and 123.7 ± 13.0 ml·min−1·1.73 m2 at 6 mo. A significant decrease of urinary albumin excretion rate was observed during the trial (basal values 219 ± 32.5 vs. 196.9 ± 28.5 μg/min at 2 mo [P < 0.05] 171.6 ± 25.5 μg/min at 4 mo [P < 0.001] and 58.6 ± 19.3 μg/min at 6 mo [P < 0.001]). No significant change in renal plasma flow was seen during tolrestat treatment. Filtration fraction significantly decreased in the tolrestat group from the basal value of 0.23 ± 0.02 to 0.21 ± 0.01 at 2 mo (P < 0.005); 0.18 ± 0.02 at 4 mo (P < 0.001); and 0.17 ± 0.02 at 6 mo (P < 0.001).

CONCLUSIONS

The polyol pathway is implicated in hemodynamic changes associated with early diabetic nephropathy, and aldose reductase treatment can positively influence these parameters.
Serum Creatinine, Height, and Weight Do Not Predict Glomerular Filtration Rate in Children with IDDM
Authors: Waz Wayne R , Quattrin Teresa , Feld Leonard G
Published: March 2007

OBJECTIVE

To assess the validity of two equations: K × height/serum creatinine (KL/Cr; K = 0.55 for females 1–18 yr of age and 0.7 for males 12–18 yr of age) and (140 – age) × weight/72 × creatinine (×0.85 for women; Cockroft-Gault) in estimating glomerular filtration rate in children and adolescents with IDDM.

RESEARCH DESIGN AND METHODS

From the records of the Children's Hospital Diabetes Clinic, we selected 70 patients with GFR determined by 99mTc-labeled DTPA plasma clearance, stable renal function, and simultaneous measurements of height, weight, blood pressure, HbA1c, and plasma creatinine. We compared DTPA-GFR with estimated GFR from KL/Cr and Cockroft-Gault equations for three groups: all patients, patients with DTPA-GFR ≤ 140 ml·min−1 · 1.73 m−2, and patients with DTPA-GFR > 140 ml·min−1 · 1.73 m−2.

RESULTS

For all patients, mean values for DTPA-GFR = 147 (95% confidence interval, 139–155), for KL/Cr = 118 (110–125), and for Cockroft-Gault = 84 ml–·min−1 · 1.73 m−2 (78–90). For patients with DTPA-GFR ≤ 140, DTPA-GFR = 123 (117–128), KL/Cr = 110 (100–119), and Cockroft-Gault = 92 (82–102). For patients with DTPA-GFR > 140, DTPA-GFR = 167 (158–177), KL/Cr = 125 (114–136), and Cockroft-Gault = 77 (71–84). Linear regression analysis showed significant (P < 0.05) relationships for KL/Cr only in patients with DTPA-GFR ≤ 140 (r = 0.29), for Cockroft-Gault in all patients (r = −0.46), and for patients with DTPA-GFR ≤ 140 (r = −0.31). Determination of a revised K for use in KL/Cr from individual calculations of K (DTPA-GFR × Cr/L) yielded an average value of 0.70 (SD = 0.11). With the use of K = 0.7, the mean KL/Cr value for patients with DTPA-GFR ≤ 140 ml·min−1 · 1.73 m−2 was 125 ± 27 (95% confidence interval, 115–135), compared with a DTPA-GFR value of 123 ± 14 (95% confidence interval, 117–128).

CONCLUSIONS

KL/Cr and Cockroft-Gault do not accurately estimate DTPA plasma clearance. We recommend the use of K equal to 0.70 when estimating GFR in children and adolescents with IDDM and DTPA-GFR ≤ 140 using KL/Cr and do not recommend the use of the KL/Cr (for patients with DTPA-GFR > 140) or the Cockroft-Gault equation in this population.