bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased Sarcoplasmic Reticulum Activity and Contractility in Diabetic db/db Mouse Heart
Authors: Belke Darrell D. , Swanson Eric A. , Dillmann Wolfgang H.
Published: March 2007

Although it is known that insulin-dependent (type 1) diabetes results in depressed contractile performance associated with diminished sarcoendoplasmic reticular Ca2+-ATPase (SERCA2a) activity, findings in insulin-resistant (type 2) diabetes suggest a less clear association. The db/db insulin-resistant mouse model exhibits decreased cardiac performance both in situ and in isolated ex vivo working hearts. In this study, contractile performance and calcium transients were measured in Langendorff-perfused hearts and isolated cardiac myocytes. Diabetic (db/db) mouse hearts demonstrated decreased rates of contraction, relaxation, and pressure development. Calcium transients from isolated myocytes revealed significantly lower diastolic and systolic levels of calcium in diabetic hearts. Furthermore, the decay rate of the calcium transient was significantly reduced in diabetic myocytes, suggesting a diminished capacity for cytosolic calcium removal not associated with a change in sodium-calcium exchanger activity. Calcium leakage from the sarcoplasmic reticulum (SR) measured using tetracaine was significantly increased in diabetic myocytes. Western blot analysis indicated only a small decrease in SERCA2a expression in diabetic mice, but a large increase in phospholamban expression. Expression of the ryanodine receptor did not differ between groups. In conclusion, the decreased contractile function observed in the db/db diabetic mouse model appears to be related to decreased calcium handling by the SR.
Electrocardiographic Repolarization Complexity and Abnormality Predict All-Cause and Cardiovascular Mortality in Diabetes
Authors: Okin Peter M. , Devereux Richard B. , Lee Elisa T. , Galloway James M. , Howard Barbara V.
Published: March 2007

Type 2 diabetes is associated with increased risk of cardiovascular (CV) and all-cause mortality. Although electrocardiographic measures of repolarization abnormality and complexity stratify risk in the general population, their prognostic value in diabetes has not been well characterized. Digital electrocardiogram (ECG) readings were acquired for 994 American Indians with type 2 diabetes. ST segment depression (STD) ≥50 μV and rate-corrected QT interval (QTc) >460 ms were examined as measures of repolarization abnormality. The principal component analysis (PCA) of the ratio of the second to first eigenvalues of the T-wave vector (PCA ratio) (>32.0% in women and >24.6% in men) was examined as a measure of repolarization complexity on the ECG. After a mean follow-up of 4.7 ± 1.0 years, there were 56 CV deaths and 155 deaths from all causes. In univariate analyses, STD, QTc, and the PCA ratio predicted CV and all-cause mortality. After multivariate adjustment for age, sex, and other risk factors, STD (hazard ratio 3.68, 95% CI 1.70–7.96) and PCA ratio (2.61, 1.33–5.13) remained predictive of CV mortality and both STD (2.36, 1.38–4.02) and QTc (2.03, 1.32–3.12) predicted all-cause mortality. Computerized ECG measures of repolarization abnormality and complexity predict CV and all-cause mortality in type 2 diabetes, supporting their use to identify high-risk individuals with diabetes.
Glucose-Induced Regulation of COX-2 Expression in Human Islets of Langerhans
Authors: Persaud Shanta J. , Burns Chris J. , Belin Véronique D. , Jones Peter M.
Published: March 2007

Cyclo-oxygenase (COX), the enzyme responsible for conversion of arachidonic acid to prostanoids, exists as two isoforms. In most tissues, COX-1 is a constitutive enzyme involved in prostaglandin-mediated physiological processes, whereas COX-2 is thought to be induced by inflammatory stimuli. However, it has previously been reported that COX-2 is the dominant isoform in islets and an insulin-secreting β-cell line under basal conditions. We have investigated the relative abundance of COX-1 and COX-2 mRNAs in MIN6 cells, a mouse insulin-secreting cell line, and in primary mouse and human islets. We found that COX-2 was the dominant isoform in MIN6 cells, but that COX-1 mRNA was more abundant than that of COX-2 in freshly isolated mouse islets. Furthermore, COX-2 expression was induced by maintenance of mouse islets in culture, and experiments with human islets indicated that exposure of the islets to hyperglycemic conditions was sufficient to upregulate COX-2 mRNA levels. Given that hyperglycemia has been reported to increase human β-cell production of interleukin-1β and that this cytokine can induce COX-2 expression, our observations of glucose-induced induction of COX-2 in human islets suggest that this is one route through which hyperglycemia may contribute to β-cell dysfunction.
Parasympathetic Blockade Attenuates Augmented Pancreatic Polypeptide But Not Insulin Secretion in Pima Indians
Authors: de Courten Barbora Vozarova , Weyer Christian , Stefan Norbert , Horton Mark , DelParigi Angelo , Havel Peter , Bogardus Clifton , Tataranni P. Antonio
Published: March 2007

There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypeptide (PP), an islet hormone considered a surrogate marker of parasympathetic nervous system (PNS) drive to the pancreas. To test if hyperinsulinemia in Pima Indians is due to increased vagal input to the β-cell, we examined the effect of PNS blockade in 17 Caucasian (aged 35 ± 8 years, body fat 23 ± 7% [mean ± SD]) and 17 Pima Indian males (aged 28 ± 8 years, body fat 29 ± 5%) with normal glucose tolerance. Each participant underwent four consecutive standardized liquid meal tests (64% carbohydrate, 22% fat, and 14% protein) during which a primed infusion of atropine was administered for 120 min at the following doses: 0, 2.5, 5, and 10 μg · kg fat-free mass (FFM)−1 · h−1. Areas under the curve for early (AUC0–30 min) and total (AUC0–120 min) postprandial insulin and PP secretory responses were calculated. Early postprandial insulin and PP secretory responses were higher in Pima Indians compared with those of Caucasians (both P = 0.01). Secretion of insulin and PP was inhibited by atropine (both P < 0.001). Increasing doses of atropine attenuated the ethnic difference in PP (P = 0.01) but not in early insulin secretory responses (P = 0.6), an effect that was not due to differences in gastric emptying rate (acetaminophen test) and/or circulating glucose. Similar results were observed for total secretory responses. These results confirm that compared with Caucasians, Pima Indians have an exaggerated PNS drive to pancreatic F-cells that secrete PP. However, the hyperinsulinemia of this population does not appear to be due to increased vagal input to pancreatic β-cells.
Adipose Tissue Expression of the Lipid Droplet–Associating Proteins S3-12 and Perilipin Is Controlled by Peroxisome Proliferator–Activated Receptor-γ
Authors: Dalen Knut Tomas , Schoonjans Kristina , Ulven Stine M. , Weedon-Fekjaer Mina Susanne , Bentzen Trine Gjesti , Koutnikova Hana , Auwerx Johan , Nebb Hilde I.
Published: March 2007

In a systematic search for peroxisome proliferator–activated receptor-γ (PPAR-γ) target genes, we identified S3-12 and perilipin as novel direct PPAR-γ target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet–associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-γ in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-γ therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-γ activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain.
Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier
Authors: Banks William A. , Coon Alan B. , Robinson Sandra M. , Moinuddin Asif , Shultz Jessica M. , Nakaoke Ryota , Morley John E.
Published: March 2007

Obesity is associated with leptin resistance as evidenced by hyperleptinemia. Resistance arises from impaired leptin transport across the blood-brain barrier (BBB), defects in leptin receptor signaling, and blockades in downstream neuronal circuitries. The mediator of this resistance is unknown. Here, we show that milk, for which fats are 98% triglycerides, immediately inhibited leptin transport as assessed with in vivo, in vitro, and in situ models of the BBB. Fat-free milk and intralipid, a source of vegetable triglycerides, were without effect. Both starvation and diet-induced obesity elevated triglycerides and decreased the transport of leptin across the BBB, whereas short-term fasting decreased triglycerides and increased transport. Three of four triglycerides tested intravenously inhibited transport of leptin across the BBB, but their free fatty acid constituents were without effect. Treatment with gemfibrozil, a drug that specifically reduces triglyceride levels, reversed both hypertriglyceridemia and impaired leptin transport. We conclude that triglycerides are an important cause of leptin resistance as mediated by impaired transport across the BBB and suggest that triglyceride-mediated leptin resistance may have evolved as an anti-anorectic mechanism during starvation. Decreasing triglycerides may potentiate the anorectic effect of leptin by enhancing leptin transport across the BBB.
Noninvasive Monitoring of Diabetes-Induced Cutaneous Nerve Fiber Loss and Hypoalgesia in thy1-YFP Transgenic Mice
Authors: Chen Yuk Shan , Chung Stephen S.M. , Chung Sookja K.
Published: March 2007

Progressive loss of pain perception and cutaneous nerve fibers are frequently observed in diabetic patients. We evaluated the feasibility of using thy1-YFP mice that express the yellowish-green fluorescent protein (YFP) in all of their sensory/motor neurons for noninvasive monitoring of cutaneous nerve fiber loss during diabetes. Fluorescent fibers in skin sections from the leg of thy1-YFP mice stained positive for the neuron-specific protein gene product 9.5 (PGP9.5), indicating that the cutaneous fluorescent fibers are indeed nerve fibers. In diabetic thy1-YFP mice, significant small cutaneous nerve fiber loss in the leg was observed at 3 months following the onset of diabetes, but loss of heat-induced pain perception occurred as early as 1 month following the onset of diabetes, indicating that functional impairment of sensory nerves precedes cutaneous nerve fiber loss. Immunostaining of skin sections of mice killed at 6 months following the onset of diabetes showed that parallel to the loss of small fluorescent nerve fibers, there was a significant decrease in fibers stained positive for calcitonin gene–related peptide, substance P, and purinoreceptor subtype in diabetic thy1-YFP mice. These mice will be useful for noninvasive monitoring of cutaneous nerve fiber degeneration and loss of heat-induced pain perception during diabetes and for the assessment of efficacy of therapeutic treatment of diabetic neuropathy.
Insulin Resistance, the Metabolic Syndrome, and Incident Cardiovascular Events in the Framingham Offspring Study
Authors: Rutter Martin K. , Meigs James B. , Sullivan Lisa M. , D’Agostino Ralph B. , Wilson Peter W.
Published: March 2007

The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.’s insulin sensitivity index (ISI0,120). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5–2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2–2.9], P = 0.003; and for ISI0,120 [both highest versus lowest quartile]: 0.5 [0.3–0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI0,120 levels were independently related to incident CVD (0.5 [0.3–0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8–2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P ≤ 0.007 in both). In conclusion, metabolic syndrome and ISI0,120 but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.
Indefinite Survival of Neonatal Porcine Islet Xenografts by Simultaneous Targeting of LFA-1 and CD154 or CD45RB
Authors: Rayat Gina R. , Gill Ronald G.
Published: March 2007

A variety of transient therapies directed against molecules involved in T-cell activation and function result in long-term islet allograft survival. However, there are relatively few examples of durable islet xenograft survival using similar short-term approaches, especially regarding highly phylogenetically disparate xenograft donors. Previous studies demonstrate that combined anti-lymphocyte function-associated antigen-1 (LFA-1) plus anti-CD154 therapy results in a robust form of islet allograft tolerance not observed with either individual monotherapy. Thus, the aim of this study was to determine whether the perturbation of anti-LFA-1, either alone or in combination with targeting CD154 or CD45RB, would promote neonatal porcine islet (NPI) xenograft survival in mice. NPI xenografts are rapidly rejected in wild-type C57BL/6 mice but reproducibly mature and restore durable euglycemia in diabetic, immune-deficient C57BL/6 rag-1−/− recipients. A short course of individual anti-LFA-1, anti-CD154, or anti-CD45RB therapy resulted in long-term (>100 days) survival in a moderate proportion of C57BL/6 recipients. However, simultaneous treatment with anti-LFA-1 plus either anti-CD154 or anti-CD45RB therapy could achieve indefinite xenograft function in the majority of recipient animals. Importantly, prolongation of islet xenograft survival using combined anti-LFA-1/anti-CD154 therapy was associated with little mononuclear cell infiltration and greatly reduced anti-porcine antibody levels. Taken together, results indicate that therapies simultaneously targeting differing pathways impacting T-cell function can show marked efficacy for inducing long-term xenograft survival and produce a prolonged state of host hyporeactivity in vivo.
Fructose Normalizes Specific Counterregulatory Responses to Hypoglycemia in Patients With Type 1 Diabetes
Authors: Gabriely Ilan , Shamoon Harry
Published: March 2007

We have previously reported that specific counterregulatory responses to hypoglycemia were augmented by an infusion of fructose in nondiabetic humans. We hypothesized that this effect was due to the interaction of a “catalytic” dose of fructose with the regulatory protein for glucokinase in glucose-sensing cells that drive counterregulation. To examine whether fructose could restore counterregulatory responses in type 1 diabetic patients with defective counterregulation, we performed stepped hypoglycemic clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l glucose steps, 50 min each) in eight intensively treated patients (HbA1c 6.4 ± 0.7%) on two separate occasions: without (control) or with coinfusion of fructose (1.2 mg · kg−1 · min−1). Fructose induced a resetting of the glycemic threshold for secretion of epinephrine to higher plasma glucose concentrations (from 3.3 ± 0.1 to 3.9 ± 0.1 mmol/l; P = 0.001) and markedly augmented the increment in epinephrine (by 56%; P < 0.001). The amplification of epinephrine responses was specific; plasma norepinephrine, glucagon, growth hormone, and cortisol were unaffected. Hypoglycemia-induced endogenous glucose production ([3-3H]-glucose) rose by 90% (P < 0.001) in the fructose studies, compared with −2.0% (NS) in control. In concert, the glucose infusion rates during the 3.9- and 3.3-mmol/l steps were significantly lower with fructose (2.3 ± 0.6 and 0.0 ± 0.0 vs. 5.9 ± 1.15 and 3.9 ± 1.0 μmol · kg−1 · min−1, respectively; P < 0.001 for both), indicating the more potent counterregulatory response during fructose infusion. We conclude that infusion of fructose nearly normalizes the epinephrine and endogenous glucose production responses to hypoglycemia in type 1 diabetic patients with impaired counterregulation, suggesting that defects in these responses may be dependent on glucokinase-mediated glucose sensing.
NOD B-cells Are Insufficient to Incite T-Cell-Mediated Anti-islet Autoimmunity
Authors: Moore Daniel J. , Noorchashm Hooman , Lin Tina H. , Greeley Siri A. , Naji Ali
Published: March 2007

Although it is well established that B-cells are required for the development of diabetes in the nonobese diabetic (NOD) mouse, the nature of their role remains unknown. Herein, we investigate the hypothesis that B-cells in this autoimmune background actively disrupt the tolerant state of those T-cells with which they interact. We demonstrate that NOD B-cells express elevated levels of crucial molecules involved in antigen presentation (including CD21/35, major histocompatibility complex class II, and CD40), alterations that invite the possibility of inappropriate T-cell activation. However, when chimeric animals are generated in which all B-cells are NOD-derived, a tolerant state is maintained. These data demonstrate that although B-cells are required for the development of autoimmunity, they are not sufficient to disrupt established tolerance. Moreover, non-B-cell antigen-presenting cells may be the critical actors in the establishment of the tolerant state; this function may be absent in NOD mice as they are characterized by deficient professional antigen-presenting cell function.
The Need for Special Foods and Sugar Substitutes by Individuals with Diabetes Mellitus
Authors: Talbot John M , Fisher Kenneth D
Published: March 2007

The need for special dietary products marketed for use by individuals with diabetes mellitus and the safety and efficacy of certain nutritive sweetener substitutes for sucrose are reviewed. Special foods for individuals with diabetes mellitus are not necessary to achieve the dietary objectives recommended by leading United States and European authorities. They can be achieved conveniently and at minimum expense through enlightened choices of commonly available food items. At present, specific and unique characteristics of food products with special therapeutic properties for diets of diabetic individuals cannot be delineated or defined on rational nutritional grounds. Such terms as “diet”, “dietetic”, and “diabetic” on food labels have no uniform meaning for consumers, and diabetologists have observed that patients tend to consume such foods without regard to their energy content. Some consumers regard the reduced-calorie and low-calorie prepared food products as convenient in diets for weight reduction and diabetes although their use in dietary management of diabetes has no therapeutic basis other than weight reduction and maintenance. When fed as pure substances to fasted subjects, the nonglucose carbohydrate nutritive sweeteners, fructose, xylitol, and sorbitol, are absorbed relatively slowly and produce less postprandial hyperglycemia and insulin response than sucrose or glucose. Adequate studies of their long-term effectiveness when ingested as part of mixed meals have not been conducted. Although these sucrose substitutes are generally considered safe, the significance of recent information on possible carcinogenicity of oral xylitol in long-term feeding studies has not been fully evaluated. In view of the lack of certain essential information on the long-term effectiveness of various diets in preventing or mitigating the chronic debilitating complication of diabetes, suggestions for future research are included.
Nutritional Management in Diabetes and Pregnancy
Authors: Franz Marion
Published: March 2007

During pregnancy it is necessary for the mother with diabetes to maintain careful control of the diabetes in order to lessen both fetal and maternal morbidity and mortality. The diet must take into account not only the metabolic requirements of the mother, but also those of the developing fetus. A total weight gain of 22 to 26 pounds is recommended, with the pattern of weight gain being more important than the total amount. Pregnancy is not a time for weight reduction. Caloric requirements can be met by the addition of 300 kcal. per day to the prepregnancy meal plan, or about 36 kcal. per kilogram. This can be met by the addition of 50 gms. carbohydrate and 30 gms. protein. Diets will contain approximately 1800 to 2500 calories a day. Calcium, iron, folic acid, and sodium also require attention in meal planning. The importance of regular meals and snacks must be emphasized. In particular, bed-time snacks are important because of the tendency towards overnight hypoglycemia and ketosis.
Evaluation of Patients' Knowledge of Diabetes Self-Care
Authors: Miller Leona V , Goldstein Jack , Nicolaisen Gary
Published: March 2007

A survey conducted at a Veterans Administration Hospital to evaluate patient capability for self-management found that over 35 per cent of the patients interviewed lacked any formal training. Seventeen patients had been placed on insulin without formal instruction. Almost one half the patients who claimed to have attended training programs could not demonstrate adequate knowledge or skills in any of the major areas of self-care: insulin administration, urine testing, diet, foot care, and management of hypoglycemia and hyperglycemia. While patients with training were more knowledgeable than patients without training, the difference was slight. The results indicate the need for systematic analysis of patient knowledge and the evaluation of training programs on a continuing basis.
Residual β-Cell Function in Children With IDDM: Reproducibility of Testing and Factors Influencing Insulin Secretory Reserve
Authors: Clarson Cheril , Daneman Denis , Drash Allan L , Becker Dorothy J , Ehrlich Robert M
Published: March 2007

Reproducibility of C-peptide secretion was assessed in 20 children (group 1) by their responses to two Sustacal- (a mixed liquid meal) stimulation tests performed 7–14 days apart. For the 12 C-peptide-positive children (basal C-peptide ≥0.03 pmol/ml) there were no differences in the basal or stimulated values between tests 1 and 2. The effect of exogenous insulin on C-peptide secretion was assessed in 20 other children (group 2) by their responses to two Sustacal tests, one test without and one with soluble insulin (0.25 U/kg) injected subcutaneously before testing. Eleven children were C-peptide positive and had no differences in C-peptide response between tests 1 and 2. The results from test 1 in groups 1 and 2 were combined with those from 44 others undergoing a single Sustacal test (group 3, N = 84). There was a close correlation between basal and peak C-peptide concentrations in the 44 C-peptide-positive children (r = .88, P < .001). Peak C-peptide concentrations correlated inversely with HbA1 (r = −.29, P < .01), insulin dose in units per kilogram (r = −.40, P < .001), and duration of diabetes (r = .33, P < .001) and positively with age at onset of diabetes (r = .34, P < .001). The C-peptide-positive children had reduced glucose response to Sustacal, lower HbA1 concentration, lower insulin requirement, later age of onset, and shorter duration of diabetes than children who were C-peptide negative.
Effect of Metformin on Insulin-Stimulated Glucose Turnover and Insulin Binding to Receptors in Type II Diabetes
Authors: Nosadini R , Avogaro A , Trevisan R , Valerio A , Tessari P , Duner E , Tiengo A , Velussi M , Del Prato S , De Kreutzenberg S , Muggeo M , Crepaldi G
Published: March 2007

Euglycemic insulin glucose-clamp and insulin-binding studies on erythrocytes and monocytes were performed in seven type II (non-insulin-dependent) diabetic subjects before and after 4 wk of metformin treatment (850 mg 3 times/day) and in five obese subjects with normal glucose tolerance. Glucose turnover was also measured at basal insulin concentrations and during hyperinsulinemic euglycemic clamps. During euglycemic insulin-glucose clamps, diabetic subjects showed glucose disposal rates of 3.44 ± 0.42 and 7.34 ± 0.34 mg · kg−1 · min−1 (means ± SD) before metformin at insulin infusion rates of 0.80 and 15.37 mU · kg−1 · min−1, respectively. With the same insulin infusion rates, glucose disposal was 4.94 ± 0.55 (P < .01) and 8.99 ± 0.66 (P < .01), respectively, after metformin treatment. Glucose disposal rates in normal obese subjects were 5.76 ± 0.63 (P < .01) and 10.92 ± 1.11 (P < .01) at 0.80 and 15.37 mU · kg−1 · min−1, respectively. Insulin maximum binding to erythrocytes in diabetics was 9.6 ± 4.2 and 5.8 ± 2.6 × 109 cells (means ± SD) before and after metformin treatment, respectively (NS). Insulin maximum binding to monocytes in diabetics was 6.2 ± 2.3 × 107 cells before and 5.0 ± 1.6% after metformin. Hepatic glucose production was higher in the diabetic patients at basal insulin levels, but not at higher insulin concentrations, and was not significantly changed by drug treatment. Basal glucose and insulin concentrations decreased with metformin. Thus, metformin treatment improved glucose disposal rate without significant effect on insulin-binding capacity on circulating cells. Basal hepatic glucose output was slightly lower after metformin treatment in view of lower (9 vs. 15 μU/ml) insulin levels, potentially indicating increased sensitivity of the liver to insulin.
No Glycemic Benefit From Guar Administration in NIDDM
Authors: Holman R R , Steemson J , Darling P , Turner R C
Published: March 2007

A randomized crossover study of 5-g guar minitablets against placebo, given three times per day with main meals for 8 wk, was done in 29 non-insulin-dependent diabetes mellitus (NIDDM) patients who had near-normal fasting plasma glucose concentrations on treatment with diet alone, additional sulfonylurea, or ultralente insulin. Guar did not reduce the excessive postprandial glycemic excursion, glycosylated hemoglobin values, basal plasma glucose concentrations, basal or incremental plasma C-peptide values, or body weight. There were few side effects with either guar or placebo therapy. Mean low-density lipoprotein cholesterol levels were significantly reduced (P < .001) by guar administration (116 ± 23 vs. 104 ± 19 mg/dl). Guar additives did not improve the excessive postprandial glycemia found in NIDDM patients in whom near-normal fasting plasma glucose levels had been obtained.
Nocturnal Insulin and C-Peptide Rhythms in Normal Subjects
Authors: Levy Isaac , Recasens Asuncion , Casamitjana Roser , Figuerola Daniel
Published: March 2007

Immunoreactive insulin and C-peptide reactive plasma levels in venous blood were studied between 0100 and 0820 h in 10 healthy volunteers to assess nocturnal endogenous insulin secretion and its peripheral extraction. Insulin secretion appeared significantly reduced after 0600 h. No correlations were observed between counterregulatory hormones and insulin secretion during this period. Plasma glucose remained stable throughout the study. An increased peripheral sensitivity to insulin after 0600 h is suggested to explain reduced secretion of insulin.
Prevalence of Diabetes Mellitus in Rural Saudi Arabia
Authors: Fatani Hassan H , Mira Siraj A , El-Zubier Ahmed G
Published: March 2007

Several studies have clearly shown the impact of modernization on the prevalence of diabetes mellitus in susceptible communities. Saudi Arabia has faced a rapid development program over the last two decades. In a recent study, we found a high prevalence of diabetes mellitus in urban Saudi Arabia. A total of 5222 rural subjects of both sexes were involved in a study of the prevalence of diabetes mellitus in the western region of Saudi Arabia. Random capillary blood glucose, body weight and height, and income were recorded. The results showed an overall prevalence of 4.3%. There was a rise of prevalence with age and higher-income groups. Prevalence also differed with sex. The overall prevalence in women (5.9%) was twice that for men (2.9%; P <.001). Obesity occurred in 41.2% of our diabetic subjects compared to 29.3% in nondiabetic subjects (P < .001). Multiple logisticregression analysis with body mass index (BMI) as the dependent variable showed that sex and income status were significant factors (P < .0001 and P < .04, respectively). When blood glucose was fixed as the dependent variable, the analysis showed that age, income, and BMI were significant factors (P < .004, P < .0001, and P < .045, respectively).
Effects of Enalapril in Insulin-Dependent Diabetic Subjects With Mild to Moderate Uncomplicated Hypertension
Authors: Passa Philippe , LeBlanc Hervé , Marre Michel
Published: March 2007

The antihypertensive efficacy of enalapril and its effects on the metabolism and kidney function were investigated in 11 insulin-dependent diabetic subjects with uncomplicated mild to moderate hypertension. During a short-term single-blind controlled trial, one daily dose of 20 or 40 mg enalapril significantly reduced both systolic and diastolic blood pressure. In the supine position, mean systolic blood pressure declined from 169 ± 6 to 142 ± 6 mmHg (P < .01) and mean diastolic blood pressure from 101 ± 1.5 to 85 ± 2 mmHg (P < .001). No changes in heart rate or postural hypotension were observed.

During 1 yr of treatment, the antihypertensive efficacy of enalapril did not decline,and no clinical side effects were observed. Inhibition by enalapril of angiotensin-converting enzyme did not modify daily insulin requirements, glycemic control, uricemia, or lipid metabolism; kalemia and the markers of diabetic nephropathy were not significantly altered. These results suggest that enalapril once daily should be used as the first step inthe treatment of diabetic patients with mild to moderate hypertension.
Longitudinal Measure of Glycemic Control and Diabetic Retinopathy
Authors: Klein Barbara E K , Moss Scot E , Klein Ronald
Published: March 2007

In a population-based study, 5431 diabetic people in southern Wisconsin who were mature at onset of diabetes were identified, and their charts were reviewed. Recent glycemic control was evaluated from these charts. An index of recent glucose control with at least three glucose determinations abstracted from the doctor's chart was constructed. A sample of 1370 of the 5431 individuals was examined as part of this study. An index of glucose control could be derived for 568 of 674 people using insulin and for 565 of 696 nonusers of insulin. Correlation of the index with the glycosylated hemoglobin obtained at the time of study was significant in insulin users and nonusers.
Plasma Immunoreactive Somatostatin Response to Arginine After Glycemic Control With Continuous Subcutaneous Insulin Infusion in Type I Diabetics
Authors: Kobayashi Tetsuro , Sawano Shinji , Itoh Tokuji , Kosaka Kinori
Published: March 2007

The effects of 3 wk of near normoglycemia by continuous subcutaneous insulin infusion (CSII) on plasma immunoreactive somatostatin (IRS) responses to arginine (0.5 g · kg−1 · 30 min−1) in seven patients with insulin-dependent diabetes mellitus (IDDM) were compared with the same patients in poor glycemic control during conventional insulin therapy (CIT) and with seven normal controls. After 3 wk of CSII treatment, mean daily blood glucose and HhA1 decreased to mean (±SE) values of 129 ± 6 mg/dl and 8.0 ± 0.1%, respectively. Plasma free-insulin levels in IDDM patients 30 min before a meal during CSII were significantly higher than those during CIT or in normal controls. Fasting mean plasma IRS levels of the IDDM patients during CSII (7.3 ±1.4 pg/ml) were not different from those during CIT (8.4 ± 1.3 pg/ml) and in normal controls (5.9 ± 0.8 pg/ml). Arginine elicited a rise in plasma IRS during CIT in all seven IDDM patients during CIT and in the normal controls, with peak values of 18.2 ± 4 . 1 and 12.5 ± 1.8 pg/ml, respectively. However, no significant increase in plasma IRS was observed in all seven IDDM patients during CSII. The integrated values of plasma IRS during the arginine-infusion study of the IDDM patients treated with CIT were significantly higher than those of the normal controls. The increased integrated values of plasma immunoreactive glucagon response to arginine observed during CIT became normalized after CSII. These results suggest that glycemic control with CSII in IDDM patients suppresses the increased plasma IRS response to arginine that occurs during CIT. The persistent hyperinsulinemia may be related to the suppressed plasma IRS response observed in IDDM patients during CSII.
Adipocyte Insulin Binding and Action in Moderately Obese NIDDM Patients After Dietary Control of Plasma Glucose: Reversal of Postbinding Abnormalities
Authors: HjØllund Elisabeth , Pedersen Oluf , Sørensen Niels Schwartz
Published: March 2007

Studies of fat cells from patients with newly diagnosed, untreated non-insulin-dependent diabetes mellitus (NIDDM) have revealed severe abnormalities in insulin action on glucose transport and metabolism. To determine whether these defects can be reversed if good glycemic control is reached by dietary treatment, eight moderately obese NIDDM subjects were studied at diagnosis and again when the patients had been in good glycemic control induced by low-energy dieting for at least 2 mo (absence of glycosuria and fasting plasma glucose <7 mM). Average body weight decreased by 8 kg (P < .05). Fasting plasma glucose decreased from 11.5 ± 1.2 to 6.9 ± 0.9 mM, whereas fasting serum insulin concentrations were unchanged. Adipocyte insulin binding at tracer concentration (15 pM, 37°C) was not changed significantly (1.94 ± 0.52 to 2.05 ± 0.62% per 30 cm2 surface area/ml). The basal (noninsulin-stimulated) glucose transport (tracer glucose concentration 5 μM) increased from 25 ± 12 to 44 ± 14 pmol · 90 min−1 · 10 cm−2 surface area (P < .02). The maximally insulin-stimulated glucose transport rate increased from 35 ± 20 to 78 ± 26 pmol/90 min (P < .01). The percentage insulin response above basal levels increased from 31 ± 40 to 89 ± 58% (P < .01). The insulin sensitivity (half-maximally stimulating insulin concentrations) was also improved (P < .05). Glucose conversion rates to total lipids increased 34 ± 62 and 65 ± 80% in basal cells and maximally insulin-stimulated cells, respectively (.2 > P > .1 , .1 > P > .05). The percentage insulin response above basal level increased from 30 ± 24 to 67 ± 52% (P < .05). The percentage insulin response above basal level of glucose conversion to CO2 also increased (P < .05). The results after diet treatment were not different from those of normal controls. We conclude that dietary treatment of moderately obese NIDDM patients that leads to good glycemic control results in reversal of the abnormalities observed in adipocytes of untreated NIDDM subjects.
Evaluation of Patients With Local Reactions to Insulin With Skin Tests and In Vitro Techniques
Authors: DeShazo Richard D , Mather Patricia , Grant William , Carrington Dean , Frentz Johnette M , Lueg Mark , Lauritano Albert A , Falholt Karen
Published: March 2007

To better understand the part played by IgE and IgG antibody in the production of dermal reactions to insulin and the usefulness of skin tests in the evaluation of these reactions, we studied 21 diabetic patients referred for evaluation of large local insulin reactions, 46 diabetic patients without local insulin reactions, and 22 healthy nondiabetic controls. Study subjects were skin tested with 15 different insulins, and the results were evaluated over 48 h. All control subjects and 41 of 46 diabetic patients without local reactions were skin-test negative to insulin. The 11% of diabetic patients who reacted had positive wheal-and-flare reactions at 20 min to animal-species insulin but negative skin tests to human insulin. Study revealed two subgroups of patients with histories of local reactions. Ten (48%) of these patients had negative skin tests to insulin. The 11% of diabetic patients who reacted had positive wheal-and-flare reactions at 20 min to animal-species insulin but negative skin tests to human insulin. Study revealed two subgroups of patients with histories of local reactions. Ten (48%) of these patients had negative skin tests to insulin. Five of this subgroup remained skin-test negative to quantities of ≥8 U insulin/skin test. Eleven (52%) of the patients formed a subgroup with positive insulin skin tests; most of these patients were skin-test positive to human insulin and to beef, pork, or both insulins as well. Although the group mean insulin-specific IgE values of this latter subgroup were significantly higher than those of any other study group, overlap of these individual IgE values did not allow separation of specific individuals with positive skin tests from those of patients on insulin without dermal reactions. IgE-to-IgG insulin-specific antibody ratios in the subgroup with histories of reactions but negative skin tests were lower (0.72—0.86) than those of the patient subgroup with positive skin tests (1.98—2.36) or diabetics without reactions (0.98–1.61). We hypothesize that patients in the subgroup with positive skin tests had a primary IgE response to insulin, whereas patients in the subgroup with negative skin tests were undergoing a change from a predominant IgE response to a predominant IgG response to insulin. We conclude that skin testing with 1 U insulin/test is a simple, sensitive, and cost-effective method to detect clinically meaningful levels of insulin-specific IgE associated with large local reactions. Furthermore, up to half of the patients referred for specialized evaluation of large local reactions will have unreproducible reactions and negative skin tests that appear to reflect a process of spontaneous desensitization.
Randomized Prospective Trial of Pure Porcine and Conventional Bovine/Porcine Insulin
Authors: Asplin Chris , Raghu Prima , Clemons Peter , Lyen Kenneth , Tatpati Olga , McKnight Barbara , Baker Lester , Guthrie Richard , Sperling Mark , Palmer Jerry
Published: March 2007

Use of pure porcine insulin versus partially purified insulin of bovine/porcine origin might be expected to have certain clinical benefits, e. g., a lower incidence of skin reactions, a lower insulin dosage, better diabetes regulation, and greater preservation of endogenous insulin secretion. To test this hypothesis, we randomly assigned 112 newly diagnosed, untreated, insulin-dependent diabetic children to therapy with either pure porcine or partially purified bovine/porcine insulin. They were followed for 1 yr, data being available on at least 90 subjects at each visit. More skin reactions were found in the group treated with the bovine/porcine insulin. This insulin was of higher antigenicity, and binding of radiolabeled insulin (mean ± SE) by serum from bovine/porcine insulin treatment was 35.5 ± 2.6 versus 16.8 ± 1.4% (P < .001) for pure porcine insulin treatment 12 mo after initiation of insulin therapy. However, throughout the 12 mo of observation the levels of glycosylated hemoglobin, insulin dosage, fasting plasma glucose, and C-peptide concentration were similar for the groups. Reported incidences of hypoglycemia and nocturia were also similar. Thus, insulin-antibody formation and skin reactions were minimized by the use of pure porcine versus partially purified bovine/porcine insulin, but no other clinical advantages were apparent.
Effect of Source of Dietary Carbohydrate on Plasma Glucose and Insulin Responses to Mixed Meals in Subjects With NIDDM
Authors: Coulston Ann M , Hollenbeck Clarie B , Swislocki Arthur L M , Reaven Gerald M
Published: March 2007

It has been demonstrated that carbohydrate-rich foods result in different plasma glucose responses when eaten alone by normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). This study was designed to test if the glycemic response to mixed meals can be altered by selecting carbohydrate-rich foods based on their glycemic potency. Consequently, three test meals were developed that should have yielded high-, intermediate-, and low-glycemic responses based on the published glycemic index of all the carbohydrate foods in the meals. The test meals were consumed by normal individuals and patients with NIDDM, and the resultant plasma glucose and insulin responses were determined. The results indicated that the plasma glucose responses after the meals did not vary as a function of their glycemic potency in either the normal or NIDDM subjects. There were no significant differences in the plasma insulin responses for either group. These results indicate that the plasma glucose response to mixed meals did not vary as a function of the calculated glycemic potencies. Therefore, the glycemic response to a mixed meal was not predicted on the basis of the published values of the glycemic index of the individual carbohydrate foods included in the meal.
Impaired Gastric Emptying in Diabetic Patients With Cardiac Autonomic Neuropathy
Authors: Buysschaert Martin , Moulart Michel , Urbain Jean Luc , Pauwels Stany , De Roy Luc , Ketelslegers Jean Marie , Lambert Andre E
Published: March 2007

The aim of our study was to measure the gastric emptying rate for a solid meal in diabetic patients who had no gastrointestinal complaints with (group 1, n = 12) or without (group 2, n = 10) cardiac autonomic neuropathy and in normal controls comparable in age and sex (group 3, n = 10). Gastric emptying rate was assessed with a sequential scintiscanning method. The percentages of the initial isotope activity remaining in the stomach at different times (20, 40, 60, 80, 100, and 120 min) after the ingestion of a Tc-99m-labeled test meal and the emptying half-time were calculated. Cardiac autonomic neuropathy was determined by the beat-to-beat variations in heart rate during deep breathing. A significant reduction of the gastric emptying rate was observed in group 1. Indeed, at 80, 100, and 120 min the percentage of residual isotope activity was 73 ± 4, 60 ± 6, and 50 ± 6% (mean ± SE), respectively, in group 1 versus 61 ± 3 (P < .05), 45 ± 4 (P < .05), and 32 ± 4% (P < .02) in group 2. In group 3, residual isotope activity was 57 ± 4 (P < .05 vs. group 1), 41 ± 4 (P < .05), and 29 ± 4% (P < .02), respectively. Emptying half-time was also longer in group 1 (121 ± 9 min) than in group 2 (95 ± 6 min, P < .05) or group 3 (90 ± 4 min, P < .02). For a given diabetic patient, there was no correlation between abnormal low gastric emptying and cardiac autonomic neuropathy. In conclusion, this study shows that in a group of diabetic patients with cardiac autonomic neuropathy, mean gastric emptying rate for solid meals is significantly impaired when compared with patients without cardiac autonomic neuropathy or normal controls, even when gastrointestinal symptoms are absent.
Miscibility of Human Semisynthetic Regular and Lente Insulin and Human Biosynthetic Regular and NPH Insulin
Authors: Olsson Per-Olof , Hans Arnqvist , Henning Von Schenck
Published: March 2007

The miscibility of human semisynthetic regular and lente insulins (Actrapid human/Monotard human) and human biosynthetic regular and NPH insulins (Humulin regular/Humulin NPH) was studied in vitro and in 16 insulin-dependent diabetic patients. In vitro a decrease of regular insulin was found immediately after mixture with semisynthetic lente insulin in proportions 1:4, 1:3, 1:2, 1:1, and 2:1. This was not found after mixture with human biosynthetic regular and NPH insulins. Free insulin and blood glucose were determined over 8 h after the morning injection of regular/lente (n = 9) or regular/NPH (n = 7) insulins in proportions used by the patients (∼ 1:2) mixed in one syringe or in separate syringes. Mixing the regular/lente preparations in one syringe immediately before injection resulted in a significant loss of the early rise in free insulin (P < .01), with a tendency to a higher free insulin in the afternoon. A corresponding change in the blood glucose profile was seen. No changes were observed in free insulin or blood glucose after mixing regular and NPH preparations compared with separate injections. We conclude that mixing human semisynthetic regular and lente insulins (Actrapid human/Monotard human) instantly results in a decrease of regular insulin, probably due to formation of a longer-acting preparation, whereas no such changes occur with human biosynthetic regular and NPH insulins (Humulin regular/Humulin NPH).
Community-Based Exercise Intervention: Zuni Diabetes Project
Authors: Heath Gregory W , Leonard Bruce E , Wilson Robert H , Kendrick Juliette S , Powell Kenneth E
Published: March 2007

Non-insulin-dependent diabetes mellitus (NIDDM) is a serious health problem among the Zuni Indians of New Mexico. In July 1983, Indian Health Service personnel initiated a community-based exercise program designed to help control NIDDM in the community. To retrospectively evaluate the effects of the exercise program, the medical records of 30 participants with NIDDM were compared with the medical records of 56 nonparticipants with NIDDM matched by age, sex, health-care provider, and duration of NIDDM. From 1 July 1983 through 1 October 1985, participants had a mean weight loss of 4 kg, whereas nonparticipants had a mean weight loss of 0.9 kg (P < .05). Participants' fasting blood glucose values dropped by a mean of 43 mg/dl, compared to a mean drop of 2 mg/dl among the nonparticipants (P < .05). Participants were significantly more likely than nonparticipants to have stopped their hypoglycemic medication (relative risk 4.2) and to have decreased their medication dosage (relative risk 2.2). These results suggest that participation in a community-based exercise program can produce significant weight loss and improvement in glycemic control among a group of Native Americans with NIDDM.
Fear of Hypoglycemia: Quantification, Validation, and Utilization
Authors: Cox Daniel J , Irvine Audrey , Gonder-Frederick Linda , Nowacek George , Butterfield John
Published: March 2007

Hypoglycemia can lead to various aversive symptomatic, affective, cognitive, physiological, and social consequences, which in turn can lead to the development of possible phobic avoidance behaviors associated with hypoglycemia. On the other hand, some patients may inappropriately deny or disregard warning signs of hypoglycemia. This study presents preliminary reliability and validity data on a psychometric instrument designed to quantify this fear: the hypoglycemic fear survey. The instrument was found to have internal consistency and test-retest stability, to covary with elevated glycosylated hemoglobin, and to be sensitive to a behavioral treatment program designed to increase awareness of hypoglycemia.