bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Physiology of Glucose Transporters
Authors: Thorens Bernard , Charron Maureen J , Lodish Harvey F
Published: March 2007

Molecular cloning of cDNA encoding the human erythrocyte facilitated-diffusion glucose transporter (GT) has elucidated its structure and has permitted a careful study of its tissue distribution and of its involvement in processes such as insulin-stimulated glucose uptake by adipose cells or transformation-induced increase in glucose metabolism. An important outcome of these studies was the discovery that additional isoforms of this transporter were expressed in a tissue-specific manner; these comprise a family of structurally and functionally related molecules. Their tissue distribution, differences in kinetic properties, and differential regulation by ambient glucose and insulin levels suggest that they play specific roles in the control of glucose homeostasis. Herein, we will discuss the structure of three members of the GT family: erythroid/brain GT, liver GT, and adipose cell/muscle GT. In the light of their tissuespecific expression, kinetic parameters, and susceptibility to insulin action, we discuss their possible specific functions.
Insulin Action in Cells Expressing Truncated or Kinase-Defective Insulin Receptors: Dissection of Multiple Hormone-Signaling Pathways
Authors: McClain Donald A
Published: March 2007

An attempt has been made to dissect insulin-signaling pathways by means of in vitro mutagenesis of the insulin receptor. Studies of two mutants are reviewed: a COOH-truncated receptor and a mutant of the ATPbinding site that is tyrosine kinase defective. The COOH-truncated receptor has normal insulin binding and normal endocytosis and undergoes autophosphorylation and activation as a kinase in vitro and in vivo. Loss of the COOH-terminal43 amino acids has, however, impaired the ability of the receptor to signal metabolic events while augmenting its ability to signal mitogenesis. Thus, domains have been partially identified that are separately involved in metabolic and mitogenic signaling, facilitating future studies of these pathways. The kinase-defective receptor is not only biologically inactive, but has a dominant inhibitory effect on the endogenous insulin receptors in the cell. That is, transfected Rat-1 cells carrying defective human receptors still have normally active rat insulin receptors but are incapable of signaling insulin action. The fact that metabolic signaling by insulinlike growth factor I (IGF-I) is intact in these cells allows definition of separate insulin and IGF-I pathways, leading to stimulation of glucose transport. Analysis of dose responsiveness for mitogenesis implies that mitogenic signaling pathways are shared by insulin and IGF-I, however. The utility of these cell lines in defining these pathways is discussed.
Insulin Gene in Diabetes Analysis Through RFLP
Authors: Permutt M Alan , Elbein Steven C
Published: March 2007

Insulin deficiency is a prominent feature of non-insulindependent (NIDDM) and insulin-dependent (IDDM) diabetes mellitus that could result from defects in the insulin gene. Cloning of this gene has permitted molecular-genetic studies including the definition of multiple-DNA-sequence polymorphisms detected with restriction endonucleases, or restriction-fragment-length polymorphisms (RFLPs), and the mapping of the insulin gene to the short arm of chromosome 11 adjacent to the insulinlike growth factor II (ICF-II) and tyrosine hydroxylase genes. The combined RFLPs for the insulin, IGF-II, and tyrosine hydroxylase genes make this a highly informative locus for genetic studies of the insulin gene in diabetes. Early studies of an RFLP consisting of variable-number tandem repeats (VNTR) of DNA near the insulin gene suggested an association of certain alleles with ∼170 copies of the repeat unit with NIDDM. Although subsequent studies in NIDDM did not confirm this association, an association of different alleles defined by ∼40 copies of the repeat unit in this VNTR region with IDDM has been demonstrated in multiple studies. This VNTR region and the multiple other RFLPs for this region have been used in linkage analysis to study the segregation of insulin genes in families. These studies have failed to demonstrate a major significant role for insulin-gene defects in NIDDM, maturity-onset diabetes of the young, or IDDM in American Blacks and Whites and under various models of inheritance. Several pedigrees with diabetes and defects of the insulin gene have been described, however, and a minor role for this gene in NIDDM cannot be eliminated from available studies. Similarly, the association studies of the insulin gene and IDDM suggest a minor modifying role undetectable in pedigree studies. The role of defects in or near the insulin gene in a small subset of NIDDM or in IDDM must await direct investigation of the insulin gene in diabetic individuals with the most recent methods for gene amplification and sequence analysis.
Frozen Desserts and Glycemic Response in Well-Controlled NIDDM Patients
Authors: Bukar Julie , Mezitis Nicholas H E , Saitas Vassiliki , Pi-Sunyer F Xavier
Published: March 2007

Fructose is known to elicit a lower glycemic response than sucrose, and high-fructose desserts have been recommended for a diabetic diet. We compared a cholesterol-free tofu-based frozen dessert (TFD) containing high-fructose corn syrups with a dairy-based sucrose-sweetened ice cream (IC). Six male and six female non-insulin-dependent diabetic patients (mean age 51 yr, mean ideal body weight 143%, fasting blood glucose <160 mg/dl) with well-controlled diabetes and managed on oral hypoglycemic agents were studied. Subjects underwent three trials. In the first trial they ingested 50 g glucose, and in the next two trials they ingested 50-g carbohydrate equivalents of either TFD or IC in random sequence. Venous blood was drawn at intervals during the 3-h trials for glucose and insulin determinations. Fasting plasma glucose was not statistically different between IC and TFD trials (130 vs. 121 mg/dl). Peak glucose responses were at 120 min in both trials (190 mg/dl for IC and 222 mg/dl for TFD), with those for TFD being significantly higher (P < 0.01). Mean glucose area and glycemic index for TFD were significantly greater than for IC (P < 0.01 and P < 0.03, respectively). There was no significant difference between mean insulin areas. In summary, the TFD, which contains soybean curd and high-fructose corn syrup, might have been expected to produce more satisfactory postprandial blood glucose levels than IC, which contains sucrose, yet a higher glycemic response was elicited. This is related to the substantial amount of total glucose in this “fructose” dessert. The study highlights the error of using individual components of a commercially prepared food to recommend a product for diabetic patients.
Testing for Blood Glucose by Office-Based Physicians in the U.S.
Authors: Harris Maureen I
Published: March 2007

A national sample of 2879 physicians were surveyed to ascertain characteristics of patient visits for diabetes including whether any test had been ordered or provided or a specimen taken to assess the patient's blood glucose level. Based on survey data, an estimated 21.3 million visits were made for diabetes in 1985. Of these, 16.8 million were for continuing care of diabetes by primary-care physicians, an average of 2.7 visits/yr for the 6.1 million U.S. residents diagnosed as having diabetes. A test for blood glucose was associated with 69% of these visits, an average of 1.9 times/yr per patient with diabetes in the U.S. Rates of testing for blood glucose varied by source of payment for the visit and were higher when diabetes was the primary diagnosis and when the number of physicians practicing together was greater, such as in health maintenance organizations or group practices. Rates of testing did not differ by age, race, or sex of the patient; location of the physician/s practice; whether insulin or oral agents were prescribed; or a number of other characteristics. Other studies indicate that self-monitoring of blood glucose is performed by <10% of diabetic patients. Hence, the physician's office remains an important location for assessment of diabetes control by measurement of blood glucose levels.
Impact of Social Support and Stress on Compliance in Women With Gestational Diabetes
Authors: Ruggiero Laurie , Spirito Anthony , Bond Andrea , Coustan Donald , McGarvey Stephen
Published: March 2007

Compliance with medical recommendations is especially important for women with gestational diabetes because of the health implications for both mother and fetus. This study examined compliance with two daily selfmanagement tasks, diet and insulin administration, in 98 women with gestational diabetes. Furthermore, the influence of stress and regimen-related social support on compliance was investigated. Results indicate that the level of reported compliance was high for both insulin administration and diet. Fewer minor stressors and greater social support were associated with greater compliance.
Increased Collagen-Linked Fluorescence in Skin of Young Patients With Type I Diabetes Mellitus
Authors: Dominiczak Marek H , Bell Jean , Cox Neil H , McCruden Douglas C , Jones Stanley K , Finlay Andrew Y , Percy-Robb Iain W , Frier Brian M
Published: March 2007

Our objective was to determine whether the fluorescence of skin collagen, which may reflect the accumulation of advanced glycosylation end products, is increased in young patients with type I (insulindependent) diabetes. Our study design was a crosssectional case-control study in a referral-based diabetic clinic in an academic hospital. Study subjects comprised a convenience sample of 18 type I diabetic patients aged 17–30 yr and 8 age-matched healthy control subjects. The fluorescence of collagen was measured in skin biopsy material. Collagen-linked fluorescence (CLF) was increased in diabetic patients (mean 10.5 [range 5.8–15.8] U/mg) compared with control subjects (7.6 [5.6–10.1] U/mg, P < 0.02). In diabetic patients, CLF was related to age (r = 0.581) and duration of diabetes (r = 0.697) but not concentration of glycosylated hemoglobin (r = 0.082). Partial correlation analysis demonstrated that duration of diabetes is the main factor determining the fluorescence of collagen in these patients. There was a relationship between CLF and presence of diabetic retinopathy after the data were adjusted for patient age and duration of diabetes (P = 0.023). Increased fluorescence of skin collagen can be detected in young type I diabetic patients and is primarily related to duration of diabetes.
Low-Pigment Skin Type and Predisposition for Development of Type I Diabetes
Authors: Ziegler Anette C , Baumgartl Hans-J , Ede Georgia , Held Martin , Vogt Hermann-J , Kolb Helmut J , Standl Eberhard
Published: March 2007

To ascertain whether skin pigmentation type and sensitivity to ultraviolet (UV) light are associated with susceptibility to type I (insulin-dependent) diabetes, 55 type I diabetic patients were examined, 38 new-onset and 17 long-term cases. They were compared to 72 control subjects of the same geographic region and nationality. To evaluate the individual skin pigmentation type, a standardized questionnaire was developed. Reactivity to UV light was determined by a stepwisegraded UV irradiation. Significantly more diabetic patients in southern Germany had blue eyes than nondiabetic control subjects (55 vs. 26%, P < 0.01), and significantly more diabetic patients had a low-pigment eye color (blue or green) than control subjects (66 vs. 38%, P < 0.01). In addition, more fair skin color was noted among diabetic versus control subjects (84 vs. 60%, P < 0.01). In response to UV irradiation, diabetic patients more often snowed an increased UV-light sensitivity than control subjects (83 vs. 23%, P < 0.001). The relative risk for susceptibility to type I diabetes in subjects with low-pigment eye color was 3.1, in subjects with fair skin type 3.4, and in subjects with increased UV-light sensitivity 5.8. The highest risk for the development of diabetes was seen in subjects who had low-pigment eye color and/or increased UV-light sensitivity (95 vs. 51%, P = 0.00002, odds ratio 17.4). We conclude that a low-pigment skin type may predispose for the development of type I diabetes.
Combination Therapy With Insulin and Sulfonylureas for Type II Diabetes
Authors: Bailey Timothy S , Mezitis Nicholas H E
Published: March 2007

Combination therapy for type II (non-insulin-dependent) diabetes mellitus with insulin and sulfonylureas has been a topic of interest since the latter were introduced to clinical use. In recent years, improved understanding of potential complications associated with hyperinsulinemia has led to resurgent interest in alternatives to insulin monotherapy for patients who have failed on a regimen of diet and sulfonylureas. A plethora of clinical trials have reported on the efficacy of oral hypoglycemic agents in limiting insulin requirements while achieving glycemic control in this subset of diabetic patients. However, few studies have been appropriate in both design and duration to provide convincing results. The randomized placebo-controlled double-blind trials that have used a parallel design and study periods of up to 1 yr have uniformly investigated second-generation sulfonylureas and yielded the most reliable information. In all instances, the combination regimen achieved reduction in insulin requirement with varying evidence of a pancreatic effect as the responsible mechanism. This treatment modality is becoming more widely accepted in the effort to achieve optimal glycemic control with minimum risk to the patient.
Cellular Mechanism of Action of Metformin
Authors: Klip Amira , Leiter Lawrence A
Published: March 2007

Metformin is a hypoglycemic drug effective in the treatment of non-insulin-dependent diabetes mellitus and increasingly used in Canada and Europe. Effects on intestinal glucose absorption, insulin secretion, and hepatic glucose production are insufficient to explain its hypoglycemic action, with most evidence suggesting that the major effect of the drug is on glucose utilization. In vivo and in vitro studies have demonstrated that metformin stimulates the insulininduced component of glucose uptake into skeletal muscle and adipocytes in both diabetic individuals and animal models. This increase is more significant in diabetic than in nondiabetic animals, suggesting an enhanced action of the drug in the hyperglycemic state. The increase in glucose uptake is also reflected in an increase in the insulin-dependent portion of glucose oxidation. Potential sites of action of metformin are the insulin receptor and the glucose transporters. Although metformin increases insulin binding in various cell types, this effect is not universal and does not correlate with stimulation of glucose utilization. In contrast, direct effects of the drug on the glucose-transport system have been demonstrated. Metformin elevates the uptake of nonmetabolizable analogues of glucose in both nondiabetic rat adipocytes and diabetic mouse muscle. In the latter, the stimulatory effect of the drug is additive to that of insulin. In human and rat muscle cells in culture, metformin increases glucose-analogue transport independently of and additive to insulin, suggesting an insulin-independent action. Most of these results suggest that the basis for the hypoglycemic effect of this biguanide is probably at the level of skeletal muscle by increasing glucose transport across the cell membrane.
Effect of Temporal Distribution of Calories on Diurnal Patterns of Glucose Levels and Insulin Secretion in NIDDM
Authors: Beebe Christine A , Van Cauter Eve , Shapiro E Timothy , Tillil Hartmut , Lyons Rachel , Rubenstein Arthur H , Polonsky Kenneth S
Published: March 2007

The effect of different temporal patterns of calorie intake on plasma glucose, serum insulin, and insulin secretion rates was examined in six patients with moderately well controlled non-insulin-dependent diabetes mellitus (NIDDM). Patients were studied on three separate occasions over 26 h. Total calories and food composition (50% carbohydrate, 15% protein, and 35% fat) were kept constant, but the pattern of calorie intake was varied. In study A (similar meal size), calories were distributed as 30, 40, and 30% at breakfast, lunch, and dinner, respectively. In study B (3 snacks, 3 meals), each subject ate three meals of 20, 20, and 30% of calories for breakfast, lunch, and dinner, respectively, and three snacks, each comprising 10% of calories, presented 2.5 h after the meal. In study C (large dinner), 10% of calories were consumed at breakfast, 20% at lunch, and 70% at dinner. Glucose, insulin, and Cpeptide concentrations were measured at 15- to 30-min intervals. Insulin secretion rates were calculated from C-peptide levels with individually derived C-peptide clearance parameters. The different eating patterns were associated with only modest differences in overall levels of glucose and insulin secretion. Daytime insulin secretion was lowest when most of the daily calorie intake occurred in the form of a large dinner. Overnight levels of glucose and insulin secretion rates did not differ for the three eating patterns, and the morning glucose levels were also unaffected by the pattern of calorie intake on the previous day. A morning rise of glucose of >0.28 mM occurred consistently only when dinner was of moderate size (30% of total calories). We conclude that if total calorie content and food composition are kept constant, overall blood glucose control is only modestly affected by the temporal pattern of food intake. The partition of food intake into meals and snacks does not improve glucose control, and a large dinner does not result in significantly higher overnight or next-morning glucose levels.
Development of IDDM After Donating Kidney to Diabetic Sibling
Authors: Riley William J , Madaren Noel K , Spillar Rebecca P
Published: March 2007

The goal of this study was to describe a patient who developed insulin-dependent diabetes mellitus (IDDM) after donating a kidney to his sibling andto suggest a possible solution to prevent such an occurrence. A 42- yr-old man was found to have islet cell autoantibodies (ICAs) as part of a screeningprogram of first-degree relatives with IDDM. Two years previously, he had donated his kidney to his HLA-identical sibling with long-standing IDDM. Both oral and intravenous glucose tolerance tests demonstrated a gradual loss of insulin secretion and increasing glucose intolerance until the patient developed IDDM 6 yr after the nephrectomy. Whether the presence of ICA is an absolute contraindication to being a kidney donor could be debated. Nonetheless, ICA should be used as a screening test to identify individuals at risk for subsequent IDDM. For those found to be positive, counseling should be provided.
Oral Contraceptives in Women With Diabetes
Authors: Klein Barbara EK , Moss Scot E , Klein Ronald
Published: March 2007

We evaluated the association of oral contraceptive use with the presence and severity of diabetic retinopathy, hypertension, and glycosylated hemoglobin in women of childbearing age who have diabetes. Neither current or past use nor number of years of use of oral contraceptives was associated with severity of retinopathy, hypertension, or current glycosylated hemoglobin. In conclusion, further study of various birth control methods in young women of childbearing age should be considered.
Metabolic Control in Diabetic Subjects in Three Swedish Areas With High, Medium, and Low Sales of Antidiabetic Drugs
Authors: Stålhammar Jan , Bergman Ulf , Boman Kurt , Dahlén Magnus
Published: March 2007

Objective

The relationship between use of antidiabetic drugs and metabolic control was studied in Swedish diabetic populations in areas with high (Gotland), medium (Tierp), and low (Skellefteå) sales of antidiabetic drugs.

Research Design and Methods

The study population consisted of 405 drug-treated diabetic subjects aged 50–74 yr. In all three areas, glyburide comprised ∼75% of the oral treatment.

Results

In accordance with sales, Gotland was found to be a heavy-use area, characterized by a high prevalence of insulin treatment (43%), combination therapy with sulfonylureas and biguanide (28%), and high prescribed daily doses (PDDs) of glyburide (15.5 ± 0.8 mg) compared with other areas. In Skellefteå, 38% were on insulin, 4% were on combination therapy, and the PDD of glyburide was 7.1 ± 0.6 mg. In Tierp, 27% were on insulin, 26% were on combination therapy, and the PDD of glyburide was 11.4 ± 0.7 mg. In Gotland, both men and women had significantly lower HbA1c levels, regardless of treatment mode, and a tendency to be more overweight compared with the area with the least pharmacological intensity (Skellefteå).

Conclusions

In the three diabetic populations, good metabolic control, defined as an HbA1c level of < 7% and acceptable weight control (body mass index < 27 for men and < 25 for women), was achieved among only 16% in Gotland, 17% in Skellefteå, and 12% in Tierp.
Change in Metabolic Control and Functional Status After Hospitalization: Impact of Patient Activation Intervention in Diabetic Patients
Authors: Rost Kathryn M , Flavin Karen S , Cole Karen , McGill Janet B
Published: March 2007

Objective

To determine whether a short intervention to enhance patient information seeking and decision making during hospitalization results in improved metabolic control and functional status in patients with diabetes mellitus.

Research Design and Methods

A randomized clinical trial was conducted in which control patients received a comprehensive 3-day evaluation and educational program, whereas experimental patients received a 45-min patient activation intervention and a 1-h self-administered booster in addition to the program. Metabolic control and functional status were measured at baseline and 4 mo postdischarge.

Results

During their discharge discussions, experimental patients asked significantly more questions than control patients (7.4 vs. 3.0, P > .001) and 4 mo later reported significantly fewer physical limitations in activities of daily living than the control group (P = 0.02). Improvement in metabolic control was statistically significant only for experimental patients (P = 0.02), although their glycosylated hemoglobin levels were not significantly lower than control patients' at follow-up. The intervention did not diminish physician satisfaction with patient interactions, although it may have increased physician frustration with responsibilities that competed with patient care.

CONCLUSIONS

These results suggest that the addition of a patient activation intervention to a comprehensive diabetes management program may substantially enhance physical functioning among adults with diabetes mellitus.
Effect of Antihypertensive Drugs on Insulin Absorption
Authors: Veenstra Jan , van der Hulst Jan P , Wildenborg Ingrid H , Njoo Suzy F , Verdegaal Wim P , Silberbusch Joseph
Published: March 2007

Objective

To examine the effects of antihypertensive drugs on the absorption of subcutaneously injected insulin.

Research Design and Methods

Eleven healthy volunteers (group 1) were given 1 mg/kg body wt propranolol three times a day during 48 h and a single dose on the morning of investigation. Seven other healthy volunteers (group 2) were given 10 mg nifedipine 30 min before subcutaneous injection of 10 U 125I-labeled soluble insulin. Absorption was measured by counting radioactivity externally. In both groups, control experiments were conducted under the same conditions without administration of propranolol or nifedipine.

Results

Propranolol usage was associated with higher mean percentages of remaining activity (P < 0.05 by analysis of variance [ANOVA]) than in the control experiment. In the nifedipine experiment, mean percentages were significantly lower compared with the control experiment (P < 0.02 by ANOVA). The mean decline in activity of all 30-min periods was 6.8 ± 3.5 vs. 3.6 ± 3.7% for control versus propranolol (group 1) (P < 0.05) and 6.3 ± 1.8 vs. 9.6 ± 3.2% for control versus nifedipine (group 2) (NS).

Conclusions

Antihypertensive drugs can influence insulin absorption. Propranolol (a peripheral vasoconstrictor) decreases insulin absorption, whereas nifedipine (a vasodilatator) increases insulin absorption.
New Semiquantitative Dipstick Test for Microalbuminuria
Authors: Bangstad Hans-Jacob , Try Kenneth , Dahl-Jørgensen Knut , Hanssen Kristian F
Published: March 2007

Objective

We compared a new semiquantitative dipstick test for microalbuminuria (Micral-Test) with a quantitative immunoturbidimetric method.

Research Design and Methods

This correlation study was performed at a pediatric and medical outpatient clinic at a university hospital. Overnight urine samples containing < 200 mg/L albumin from 186 diabetic patients were analyzed.

Results

The correlation coefficient between the new semiquantitative method and the immunoturbidimetric reference method was 0.82. Elevated albumin concentration was defined as > 20 mg/L albumin in overnight urine, and the prevalence of samples with values above this level was 28%. By this definition, the Micral-Test assay level > or equal to 20 mg/L had a sensitivity of 92.3% and a specificity of 82.1%. Of the diabetic subjects, 84.9% were correctly classified as having elevated urinary albumin concentration or not.

Conclusions

The Micral-Test is useful for in-clinic screening for elevated urinary albumin concentration and monitoring the development of urinary albumin excretion in the low microalbuminuric range.
Comparison of Incidence of IDDM in Childhood Between Estonia and Finland, 1980–1988
Authors: Tuomilehto Jaakko , Podar Toomas , Reunanen Antti , Kalits Irina , Lounamaa Raisa , Tuomilehto-Wolf Eva , Adojaan Bela , Neff Barbara , LaPorte Ronald E
Published: March 2007

Objective

To compare nationwide incidence of childhood insulin-dependent diabetes mellitus (IDDM) in children aged 0-14 yr between Estonia and Finland during 1980-1988. For Estonia, which has a population genetically and linguistically related to Finland, only limited information was available. Finland has the highest incidence of IDDM in the world.

Research Design and Methods

The registration of all new cases of IDDM in Estonia was conducted by the local district pediatricians who reported every newly diagnosed diabetic patient to the Republic Endocrinology Centre. Registration of all new cases of IDDM in Finland was based on the statistics of the Social Insurance Institution, which approves free-of-charge insulin treatment for diabetes. These data were validated with one or more additional data sources. The case ascertainment rate approached 100% in both countries.

Results

The average yearly incidence of IDDM standardized for age for the years 1980–1988 in Estonia was ~ 33% of that in Finland. Among males it was 11.3 (95% confidence interval [CI] 10.3–12.3) per 100,000 in Estonia and 35.1 (95% CI 33.4–36.9) per 100,000 in Finland, and among females 10.1 (95% CI 9.2–11.1) per 100,000 in Estonia and 30.4 (95% CI 28.8–32.1) per 100,000 in Finland. When the two periods 1980–1982 and 1986–1988 were compared, the age-standardized incidence in Estonia remained unchanged, whereas in Finland it increased ~ 20%.

Conclusions

The data between two populations who are ethnically and linguistically similar and live geographically close but in a different environment, provides further evidence that both genetic and environmental factors are contributing to the risk of IDDM.
Energy and Substrate Metabolism in Obesity and Postobese State
Authors: Tappy Luc , Felber Jean P , Jéquier Eric
Published: March 2007

The total energy expenditure (EE) of human beings is represented by basal metabolic rate (which corresponds to 60-70% of EE), dietary-induced thermogenesis (10% of EE), and the energy expended in physical activity (20-30% of EE). Obese individuals have an increased total EE compared with lean subjects; this increase is essentially due to an increased lean body mass concomitant with obesity, and is completely reverted after weight loss. Glucose-induced thermogenesis (GIT), measured during an oral glucose tolerance test (OGTT) or hyperinsulinemic-euglycemic clamps, has been found to be decreased in obese individuals, although some discrepancy exists between studies. The observed decreases in GIT show a gradation, increasing progressively from obese patients with normal glucose tolerance to obese patients with impaired glucose tolerance (IGT) to obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and an increased insulin response after OGTT to obese patients with NIDDM and a hypoinsulinemic response after OGTT. The defect in GIT appears to be related to impairment in nonoxidative glucose storage and with the degree of insulin resistance. Obese patients after weight loss show a further decrease in GIT after OGTT or during a euglycemic clamp, which remains unclear. Obese patients have an increased basal lipid oxidation and a decreased suppression of lipid oxidation after OGTT or during a euglycemic clamp. Glucose oxidation and storage are both markedly decreased during a euglycemic clamp. In contrast, the defect in glucose storage is less apparent after OGTT, due to the compensatory effect of hyperglycemia and hyperinsulinemia.Infusion of triglycerides in lean nondiabetic individuals increases plasma free-fatty acid concentration and lipid oxidation and decreases insulin-mediated glucose oxidation and storage during a euglycemic clamp. Hyperglycemia under these conditions restored both glucose oxidation and storage to their initial values. Thus, an increase in lipid oxidation produces in lean individuals the metabolic alterations observed in obese patients.
Influence of Dietary Protein Intake on Whole-Body Protein Turnover in Humans
Authors: Garlick Peter J , McNurlan Margaret A , Ballmer Peter E
Published: March 2007

Methods for measuring rates of protein synthesis and degradation in the whole body of humans with isotopes of carbon and nitrogen are described and attention is drawn to their relative merits and drawbacks for studying the nutritional control of protein metabolism. A review of published work on dietary protein and protein metabolism leads to the conclusion that protein is the major dietary determinant of whole-body protein turnover rates, and that energy intake is comparatively unimportant. Dietary protein affects protein turnover at two levels: an immediate response to the intake of protein in meals and a longer-term adaptation after a change in protein intake. An increase in the level of dietary protein enhances the response to meals, which mainly consists of a decrease in the rate of protein degradation. The adaptation to higher protein intakes involves an increase in the basal (postabsorptive) rates of both synthesis and degradation. Suggestions for future investigation include more detailed studies of the acute and adaptive responses, to facilitate understanding of dietary protein requirements, and the effects of very-high-protein intakes with continued development of techniques for studying protein turnover in individual tissues in humans.
von Willebrand Factor and Endothelial Abnormalities in Diabetic Microangiopathy
Authors: Porta Massimo , La Selva Macro , Molinatti Pia A
Published: March 2007

We briefly summarize current knowledge on 1) the abnormalities of von Willebrand factor (vWF) as an indicator of endothelial cell (EC) dysfunction in diabetes and 2) the modifications induced in the growth of cultured ECs by high glucose in the incubation media. A MEDLINE search (1986 through Sept. 1989) was performed to update previous relevant references on vWF and ECs in healthy and diabetic subjects. Main data in the literature and personal contributions were scrutinized. Study quality, information, and relevance to the subject were assessed. vWF is synthesized and stored mainly in ECs. Its plasma levels are increased in diabetic microangiopathy but are not influenced by circulating glucose, insulin, or growth hormone, nor do they acutely affect platelet function in diabetes. Supraphysiological concentrations of glucose inhibit the replication of cultured ECs from large vessels via different possible mechanisms but appear to stimulate pathways involved in the activation of capillary ECs. vWF is a possible marker of EC damage in diabetes, and prospective studies will ascertain its role as a predictor for the development of microangiopathy. The possible dichotomy in the response of cultured ECs from large and small vessels to high glucose in the culture media may help explain some of the lesions observed in the walls of arteries and capillaries in diabetes.
Bacteremia in Adult Diabetic Patients
Authors: Leibovici Leonard , Samra Zmira , Konisberger Hanna , Kalter-Leibovici Ofra , Pitlik Silvio D , Drucker Moshe
Published: March 2007

objective

To compare the microbiology, sources, complications, and outcome of bacteremia in diabetic and nondiabetic patients.

Research Design and Methods

A prospective study was conducted of all episodes of bacteremia in hospitalized diabetic and nondiabetic patients. The study consisted of patients ≥ 18 yr of age with bacteremia detected within a 19-mo interval.

Results

We compared 124 episodes of bacteremia in 119 diabetic patients to 508 episodes in 480 nondiabetic patients. Diabetic patients were older than nondiabetic patients (median age 74 vs. 68 yr, P = 0.0001). In patients with an indwelling urinary catheter and bacteremic urinary tract infection, the percentage of Klebsiella in diabetic patients was 60% (6 of 10) and in nondiabetic patients was 17% (4 of 23, P = 0.04). In patients without an obvious source of bacteremia, the percentage of staphylococcal isolates in diabetic patients was 29% (10 of 35) and in nondiabetic patients was 14% (24 of 176, P = 0.04). Staphylococci were a common cause of bacteremic infections of the extremities in diabetic patients (12 of 19, 63%) and nondiabetic patients (20 of 50, 40%). Septic shock was the only complication that was more common in diabetic patients. The mortality in diabetic and nondiabetic patients was 28 and 29%, respectively.

Conclusions

Our results represent elderly patients with non-insulin-dependent diabetes mellitus. In this group, empirical treatment for suspected bacteremic urinary tract infection in patients with a urinary catheter should include coverage for Klebsiella. Empiric treatment for suspected bacteremia of unknown origin or caused by infection of the extremities should include an antistaphylococcal drug. The prognosis of bacteremia in diabetic and nondiabetic patients was similar.
Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease
Authors: DeFronzo Ralph A , Ferrannini Eleuterio
Published: March 2007

Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
Central Role of Sodium in Hypertension in Diabetic Subjects
Authors: Weidmann Peter , Ferrari Paolo
Published: March 2007

The common association between diabetes mellitus and hypertension may be promoted by several mechanisms. Patients with insulin-dependent (type I) diabetes and prone to develop nephropathy often have a familial predisposition for essential hypertension, whereas normotensive healthy offspring of nondiabetic essential hypertensive parents tend to have a reduced insulin sensitivity and increased plasma insulin levels. Na+ retention occurs as a characteristic alteration in type I or non-insulin-dependent (type II) diabetes; exchangeable body Na+ (Naex) is increased by 10% on average. This abnormality develops in the uncomplicated stage of diabetes and differentiates diabetic from nondiabetic essential hypertensive subjects. Possible Na(+)- retaining mechanisms include increased glomerular filtration of glucose leading to enhanced proximal tubular Na(+)-glucose cotransport, hyperinsulinemia (which activates several tubular Na+ transporters), an extravascular shift of fluid with Na+, and, once it occurs, renal failure. The pathogenetic role of Na+ retention in diabetes-associated hypertension is supported by positive correlations between systolic or mean blood pressure and Naex and by normalization of blood pressure after removal of excess Na+ by diuretic treatment in hypertensive diabetic subjects. The latter may also have an enhanced sensitivity of blood pressure to Na+. Plasma levels of active renin, angiotensin II, aldosterone, and catecholamines are usually normal or low in metabolically stable type I or type II diabetes. However, an exaggerated vascular reactivity to norepinephrine and angiotensin II commonly occurs already at uncomplicated stages of type I or type II diabetes. This may be a manifestation of functional (i.e., intracellular electrolytes) and/or morphological (proliferation, narrowing, and stiffening) vasculopathy. Diabetes-associated Na+ retention, vasculopathy, and a presumably inherited predisposition for both diabetes and essential hypertension may represent important complementary factors favoring the frequent occurrence of hypertension in the diabetic population.
Lipoprotein(a) Levels in Black and White Children and Adolescents With IDDM
Authors: Levitsky Lynne L , Scanu Angelo M , Gould Samuel H.
Published: March 2007

Objective

To examine the relationship between levels of lipoprotein(a) [Lp(a)], diabetes, and glycemic control in white and black nondiabetic control and insulindependent diabetic (IDDM) children and adolescents, fasting blood analyses were conducted on a subject sample drawn from referral-based diabetes and endocrine clinics and a primary-care general pediatric clinic.

Research Design and Methods

Thirty-six white and 16 black children with IDDM who volunteered to participate in this study were compared with 30 white and 42 black nondiabetic control children.

Results

Lp(a) protein levels were significantly higher (P < 0.05) in both groups of black children compared with whites (black vs. white nondiabetic children 6.8 ± 0.95 vs. 3.1 ± 0.68 mg/dl and black vs. white diabetic children 7.5 ± 1.52 vs. 3.0 ± 0.64 mg/dl). Lp(a) protein levels directly correlated with the level of glycosylated hemoglobin (r = 0.46, P < 0.01) in white diabetic children but not in black diabetic children. Well-controlled white diabetic children (n = 12, glycosylated hemoglobin <10%) had a mean Lp(a) protein level of 1.4 ± 0.3 mg/dl compared with poorly controlled white diabetic children (n = 10, glycosylated hemoglobin >13%) whose mean Lp(a) protein level was 5.7 ± 1 . 7 mg/dl (P < 0.01).

Conclusions

We conclude that circulating levels of Lp(a) protein are increased in hyperglycemia. A genetically determined elevated level of Lp(a) is a risk factor for atherosclerotic disease in white and Asian adults. Elevated Lp(a) should be investigated as an independent risk factor for atherosclerotic disease in IDDM. It could prove to be an additional mechanism for the development of diabetic complications in selected populations.
Diagnosis of Gestational Diabetes in Early Pregnancy
Authors: Super Dennis M , Edelberg Stuart C , Philipson Elliot H , Hertz Roger H , Kalhan Satish C
Published: March 2007

Objective

To determine whether glucose intolerance can be identified early in gestation in a high-risk population so that early intervention can be planned to prevent associated morbidity.

Research Design and Methods

After appropriate dietary preparation, patients with a high risk for gestational diabetes underwent a 50-g oral glucose screening test during fasting. Patients were tested on enrollment and every 10 wk until delivery. Those with a 1-h plasma glucose value of ≥7.5 mM underwent a 100-g oral glucose tolerance test. Gestational diabetes was based on either a markedly abnormal 50-g screening test or abnormal 100-g oral glucose tolerance test.

Results

Ten of 15 (66%) patients who developed gestational diabetes were diagnosed during the first half of the pregnancy. Six were diagnosed in the first trimester. If the definition of an abnormal 1-h plasma glucose value was lowered from 7.5 to 7.2 mM, an additional 2 patients could have been identified in the first trimester with an improvement in sensitivity from 70 to 91% with only a slight drop in specificity (from 91 to 88%). Diagnosis of gestational diabetes was not enhanced by measuring plasma insulin concentrations or insulin-glucose molar ratios.

Conclusions

The diagnosis of gestational diabetes in a high-risk population can be made in the first half of pregnancy. Early diagnosis should permit evaluation of intervention strategies, which may result in improved perinatal outcome.
Decrease of Lipoprotein(a) With Improved Glycemic Control in IDDM Subjects
Authors: Haffner Steven M , Tuttle Katherine R , Rainwater David L
Published: March 2007

Objective

Recently, lipoprotein(a) [Lp(a)] has been identified as a major risk factor for coronary heart disease. There are few data available on the influence of metabolic control on plasma Lp(a) concentrations in subjects with insulin-dependent diabetes mellitus (IDDM), a group at high risk for coronary heart disease.

Research Design and Methods

We examined the effects of improved metabolic control on plasma lipid and lipoproteins and Lp(a) concentrations in 12 subjects before and after 21 days of tight metabolic control.

Results

Glycosylated hemoglobin declined from 8.4 to 6.9% (P < 0.001), and Lp(a) declined from 29.7 to 27.1 mg/dl (P = 0.022). There were no significant differences in total, low-density lipoprotein, or highdensity lipoprotein cholesterol, although the decline in triglyceride concentrations were borderline statistically significant. The distribution of apolipoprotein(a) isoforms in IDDM patients was not unusual, and the apolipoprotein(a) isoform phenotypes did not change with improved metabolic control. Lp(a) concentrations were also significantly higher than in a population-based control group of nondiabetic subjects from the San Antonio Heart Study.

Conclusions

Although the number of subjects was small and the degree of improvement in metabolic control was modest, the results suggest that improved metabolic control may decrease the risk of coronary heart disease mediated by Lp(a) in IDDM.
Double-Blind Evaluation of Efficacy and Tolerability of Metformin in NIDDM
Authors: Dornan Timothy L , Heller Simon R , Peck Gillian M , Tattersal Robert B
Published: March 2007

Objective

To test the efficacy and tolerability of metformin.

Research Design and Methods

An 8-mo double-blind placebo-controlled parallel-group trial was performed at University hospital diabetic clinics on 60 patients with non-insulin-dependent diabetes mellitus (NIDDM) treated by diet alone. Metformin was administered and built up to a maximum dosage of 1 g three times daily.

Results

Mean HbA1 fell from 11.7 ± 0.4 to 10.3 ± 0.4% (means ± SE) on metformin but rose from 11.8 ± 0.4 to 13.3 ± 0.4% on placebo (P <0.001). Final mean fasting blood glucose was 5.1 mM lower with metformin than placebo (P <0.001). No other biochemical variable differed significantly, and weight did not change. A favorable glycemic response was not restricted to the obese. The mean final dosage of metformin was 1.7 ± 0.1 g and was well tolerated.

Conclusions

Metformin achieved a 23% lower mean HbA1 than placebo without weight gain or significant unwanted effects.
Severe Hypoglycemia in Type I Diabetic Patients With Impaired Kidney Function
Authors: Mühlhauser Ingrid , Toth Gisela , Sawicki Peter T , Berger Michael
Published: March 2007

Objective

To assess the frequency and possible risk indicators of severe hypoglycemia in insulin-dependent (type I) diabetic patients with impaired kidney function.

Research Design and Methods

Retrospective follow-up examination of case subjects and control subjects with mean follow-up periods of 2.9 and 1.3 yr, respectively. The setting was the diabetes center at the Düsseldorf University hospital. Subjects were consecutive type I diabetic patients. Case subjects consisted of 44 patients with initial serum creatinine levels of ≥133 μM and pathological proteinuria. Control subjects consisted of 46 patients with normal serum creatinine levels matched for age, duration of diabetes, and hypertension; 57% of case subjects and 67% of control subjects were being treated with p-blockers. Incidence of severe hypoglycemia (cases/patient-yr) was assessed through an interviewer-administered questionnaire.

Results

At comparable levels of HbA1c (7.9 ±1.8 vs. 7.6 ± 1.1%), case subjects had a fivefold higher incidence of severe hypoglycemic episodes (1.28 vs. 0.25 cases/patient-yr, P <0.02) than control subjects. Within the group with impaired kidney function, patients with severe hypoglycemic episodes had lower HbA1c levels (7.4 ± 1.6 vs. 8.7 ± 2.0%, P <0.03) and a lower body mass index (22.0 ± 3.4 vs. 24.4 ± 3.8 kg/m2 P <han those without severe hypoglycemic episodes, whereas serum creatinine levels, body weight-related insulin dosage (U kg−1 day−1), prevalence of blindness, autonomic neuropathy, and treatment with β-blockers were comparable.

Conclusions

Type I diabetic patients with impaired kidney function are at an excessively high risk of severe hypoglycemia. In addition to low HbA1c levels, a low body mass index appears to be a risk indicator for this adverse effect of insulin therapy.