bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Changing Amount of Carbohydrate in Diet on Plasma Lipoproteins and Apolipoproteins in Type II Diabetic Patients
Authors: Rivellese Angela A , Ciacco Rosalba , Cenovese Salvatore , Patti Lidia , Marotta Gennaro , Pacioni Delia , Annuzzi Giovanni , Riccardi Gabriele
Published: March 2007

Eight type II (non-insulin-dependent) normolipidemic diabetic patients (aged 45 ± 15 yr, body mass index 22 ± 2 kg/m2, means ± SD) treated with diet alone or diet plus oral hypoglycemic agents were given, in random order for periods of 15 days, two diets with different carbohydrate (CHO) (40 vs. 60% of total calories) and fat (20 vs. 40%) levels. Simple CHO, fiber, saturated fat, cholesterol, and polyunsaturated-saturated fat ratio were similar in the two diets. Total plasma cholesterol was not significantly affected by dietary changes; conversely, plasma triglyceride (1.38 ± 0.59 vs. 1.11 ± 0.39 mM, P < 0.05) and apolipoprotein Cll (3.8 ± 1 · 4 vs, 3.3 ± 0.8 mg/dl) increased significantly after the high-CHO low-fat diet. Among the various lipoproteins, very-low-density lipoprotein (VLDL) was the most affected by diet: VLDL cholesterol concentrations increased from 0.30 ± 0.19 to 0.43 ± 0.28 mM (P < 0.05), and triglyceride concentrations increased from 0.62 ± 0.33 to 0.88± 0.53 mM (P <0.05). In conclusion, increasing the amount of complex CHO in the diet induces an elevation of VLDL in normolipidemic, nonobese, mildly type II diabetic patients.
Hybrid Insulin Receptors: Molecular Mechanisms of Negative-Dominant Mutations in Receptor-Mediated Insulin Resistance
Authors: Whittaker Jonathan , Soos Maria A , Siddle Ken
Published: March 2007

Certain syndromes of extreme insulin resistance are the result of negative-dominant mutations of the insulin receptor. The insulin-receptor heterotetramer appears to be the minimal functional unit for insulin signal transduction probably due to a requirement for intersubunit interactions. The observation that insulin and insulinlike growth factor I receptors can be found in hybrid heterotetramers suggests that insulin receptors can be composed of heterodimers that are the products of separate genes. Such a structure provides a potential molecular mechanism for negative-dominant receptor mutations.
Physiology and Pathophysiology of Insulin Secretion
Authors: Rasmussen Howard , Zawalich Kathleen C , Ganesan Shridar , Calle Roberto , Zawalich Walter S
Published: March 2007

Mechanisms by which various classes of extracellular signals regulate insulin secretion are discussed regarding their cellular and molecular actions. Under physiological circumstances, the small postprandial changes in plasma glucose concentrations (∼4.4–6.6 mM) primarily serve as a conditional modifier of insulin secretion and dramatically alter the responsiveness of islets to a combination of neurohumoral agonists. These agonists have two functions. Cholecystokinin (CCK) and acetylcholine activate the hydrolysis of polyphosphoinositides, and gastric inhibitory polypeptide (GIP) and glucagonlike peptide 1 activate adenylate cyclase. These two functional classes of neurohumoral agonists act synergistically to enhance insulin secretion when plasma glucose is >6.0 mM but not when it is ≤4 mM. On the other hand, an increase in plasma glucose concentration to 8–10 mM induces an increase in insulin secretory rate in the absence of any of the neurohumoral agonists. Remarkably, high glucose leads to an increase in the same intracellular signals, as does a combination of acetylcholine and GIP. On the basis of these data, a model of how insulin secretion is regulated under physiological circumstances is proposed. This model emphasizes that the regulation of insulin secretion occurs in three stages: cephalic, early enteric, and later enteric. In this view, the crucial event occurring during the first two phases is the agonistinduced translocation of protein kinase C (PKC) to the plasma membrane under conditions in which an increase in Ca2+ influx does not occur. PKC is now in a cellular location and a Ca2+-sensitive conformation such that an increase in Ca2+ influx rate occurring during the third phase leads to its immediate activation and an enhanced rate of insulin secretion. Furthermore, under physiological circumstances, an optimal insulin secretory response is dependent on a correct temporal pattern of signals arising from neural and enteric sources. If this pattern is deranged, an abnormal pattern of insulin secretion is observed. An important new insight is provided by the observation that agonists (e.g., CCK or acetylcholine) that act to stimulate the hydrolysis of phosphatidylinositides, when acting for a short period (10–20 min), induce an enhanced responsiveness of islets to glucose, i.e., proemial sensitization. However, when acting unopposed for several hours, these agonists will induce a time-dependent suppression of responsiveness to glucose and other agonists. The latter observation implies that optimal insulin secretion is dependent on periodic rather than continuous exposure to the correct pattern of extracellular signals. The clinical implications of these new observations are discussed regarding glucose toxicity, the possible role of interleukin 1 in the pathogensis of insulin-dependent diabetes, sulfonylurea therapy, and the abnormalities of insulin secretion seen in non-insulin-dependent diabetes.
Cough Test to Assess Cardiovascular Autonomic Reflexes in Diabetes
Authors: Cardone Claudio , Paiusco Paola , Marchetti Giampaolo , Burelli Francesco , Feruglio Maria , Fedele Domenico
Published: March 2007

Coughing induces cardioacceleratory responses under cholinergic control. The Cough Test (CT), a standardized test that uses a series of coughs with electrocardiographic monitoring, was used to assess the functional integrity of cardiovascular autonomic nerves. In 224 control subjects and 235 diabetic patients, heart-rate (HR) responses were compared with four established tests: lying to standing (LS), standing to lying (SL), deep breathing (DB), and Valsalva maneuver (VM). In control subjects, HR responses declined significantly with age in a curvilinear pattern. Logtransformed indices were used to estimate percentiles. The CT-HR responses were reproducible and significantly associated with other HR-response tests. Sixty-nine (29%) diabetic patients had an abnormal value ≤1st percentile, whereas only 2 control subjects had such an abnormality. Among diabetic patients, age and duration of diabetes exerted a significant negative influence. With the use of the criteria of two abnormal or one abnormal and two borderline tests (among CT, LS, SL, DB, or VM) as a minimal criteria for cardiovascular autonomic neuropathy, CT and LS had the least overlap between the control and diabetic populations and were significantly better than SL or VM (P < 0.005 for CT, P < 0.01 for LS). They were not different from DB. We found the CT to be simple to perform, reproducible, and useful for the assessment of cardiovascular autonomic reflexes.
Screening for Thyroid Disease in Children With IDDM
Authors: McKenna Malachi J , Herskowitz Raymonde , Wolfsdorf Joseph I
Published: March 2007

The aim of this study was to evaluate the usefulness of screening for thyroid disease by performing thyroid function tests and measuring thyroid autoantibodies in 371 children and adolescents with insulin-dependent diabetes mellitus (IDDM). We analyzed clinical data and results of serum thyroxine, triiodothyronine uptake, thyroid-stimulating hormone, and antibodies to thyroid microsomal antigen and thyroglobulin. Goiter was noted in 20% of subjects. Thyroid-specific autoantibody was positive in 19% of subjects. Twenty-seven subjects (7%) had thyroid dysfunction. Autoantibody testing identified subjects with thyroid dysfunction with a sensitivity of 50%, a specificity of 84%, a degree of misclassification of 17%, a positive predictive value of 13%, and a negative predictive value of 97%. We recommend that all children and adolescents be screened shortly after diagnosis of IDDM by determination of thyroid-stimulating hormone (measured by high-sensitivity assay) to identify thyroid dysfunction and by testing for antibody to thyroid microsomal antigen to characterize both risk of future thyroid dysfunction and the need for future testing.
Diabetes, Hyperinsulinemia, and Hyperlipidemia in Small Aboriginal Community in Northern Australia
Authors: O'Dea Kerin , Lion Robin J , Lee Amanda , Traianedes Kathy , Hopper John L , Rae Cheryl
Published: March 2007

A small rural Aboriginal community in northern Australia was surveyed for diabetes, impaired glucose tolerance (IGT), hyperinsulinemia, and lipid levels. Of the 122 adults >17 yr of age who participated (95% response rate), 11.5% had diabetes, 7.4% had IGT, and the remaining 81.1% had normal glucose tolerance. Both diabetes and IGT were strongly age related. This high frequency of diabetes occurred, despite the population being relatively lean. Although the body mass index (BMI) increased with age in both men and women, only 25% of the population overall had BMI >25 kg/m2. There were wide ranges of insulin responses to glucose, with the upper fertile of 2-h insulin levels being more than seven times higher than the lower fertile (144 ± 13 vs. 19 ± 1 mLI/L). Hyperinsulinemia was associated with IGT, elevated triglycerides, and lower high-density lipoprotein cholesterol levels. Lipid abnormalities were much more frequent among men than women. Cholesterol levels were an average of 0.55 mM higher and triglycerides an average of 1.05 mM higher in men than in women, and both increased with age. In conclusion, this small isolated Aboriginal population from northern Australia had an unexpectedly high frequency of diabetes (in view of their relative leanness) in association with a high frequency of metabolic abnormalities indicative of insulin resistance (hyperinsulinemia, IGT, hypertriglyceridemia).
Visual Impairment and Retinopathy in People With Normal Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed NIDDM
Authors: Klein Ronald , Barrett-Connor Elizabeth L , Blunt Barbara A , Wingard Deborah L
Published: March 2007

Objective

Prevalence rates of visual impairment and retinopathy were compared in 1992 people with normal glucose tolerance, impaired glucose tolerance (IGT), or newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM).

Research Design and Methods

Glucose tolerance status was based on an oral glucose tolerance test after exclusion of those with a history of diabetes and/or diabetes medication use in an upper middle-class community of older white adults in southern California between 1984 and 1987.

Results

Although many sex-specific comparisons were made between glucose tolerance groups, only a few emerged as statistically significant. Among those, women with IGT had significantly higher age-adjusted rates of visual impairment (10.8%) than women with normal glucose tolerance (4.4%). Among men, those with IGT had significantly higher age-adjusted rates of visual impairment (7.9%) than men with newly diagnosed NIDDM (4.0%).

Conclusions

Low frequencies of retinopathy were found in all three glucose tolerance groups.
Patterns of Glucose and Lipid Abnormalities in Black NIDDM Subjects
Authors: Chaiken Rochelle L , Banerji Mary Ann , Pasmantier RoseMarie , Huey Howard , Hirsch Sondra , Lebovitz Harold E
Published: March 2007

Objective

We had previously shown two variants among black non-insulin-dependent diabetic (NIDDM) subjects in a normoglycemic remission: one with insulin resistance and the other with normal insulin sensitivity. This study examined whether these two variants exist in the ordinary hyperglycemic black NIDDM population.

Research Design and Methods

Fifty-two black NIDDM subjects were assessed for insulin-stimulated glucose disposal (euglycemic clamp), glycemic control (fasting plasma glucose and HbA1c), and fasting lipid profiles.

Results

The distribution of glucose disposal in 30 black NIDDM subjects (body mass index; BMI < 30 kg/m2) was bimodal, which indicated two populations. Eighteen of 30 subjects (BMI 26.4 ± 0.5 kg/m2) had insulin resistance (glucose disposal 3.21 ± 0.24 mg·kg−1·min−1). Twelve of 30 subjects (BMI 24.83 ± 1.1 kg/m2) had normal insulin sensitivity (glucose disposal 7.19 ± 0.46 mg·kg−1·min−1). Twenty-one of the remaining 22 subjects (BMI 33.4 ± 0.7 kg/m2) were insulin resistant (glucose disposal 2.88 ± 0.21 mg·kg−1·min−1). Fasting serum triglyceride levels were lowest in the insulin-sensitive population (0.91 ± 0.07 mM) and different from the insulin-resistant population, BMI < 30 and > 30 kg/m2, (1.20 ± 0.10 mM, P < 0.05 and 1.42 ± 0.17 mM, P < 0.025, respectively). Fasting serum low-density lipoprotein cholesterol levels were not significantly different among the groups, although it did increase with insulin resistance and increasing obesity. Total serum cholesterol levels and glycemic control were similar for all three groups. Serum high-density lipoprotein cholesterol levels were higher in women compared with men.

Conclusions

In the hyperglycemic black NIDDM population, two variants exist: one with insulin resistance and one with normal insulin sensitivity. This insulin-sensitive variant represents 40% of subjects with a BMI < 30 kg/m2. Moreover, the insulin-sensitive group has a lower risk profile for cardiovascular disease.
Factors Determining Recall of Examination Results in Diabetic Population
Authors: Moss Scot E , Klein Ronald , Klein Barbara EK
Published: March 2007

Objective

To determine factors influencing recall of examination results after 4 yr.

Research Design and Methods

At two examinations that were 4 yr apart, a diabetic population was asked, “Have you been told that your diabetes has affected the back of your eyes, that is the retina?” Participants were informed by letter whether they had retinopathy. Subjects in this study included younger-onset (n = 311) and older-onset (n = 279) diabetic subjects who had retinopathy at baseline and did not know it.

Results

Forty-two percent of younger-onset and 29% of older-onset subjects recalled at follow-up that they had been told their diabetes had affected their eyes. People in both groups were more likely to recall they had retinopathy if they had more severe retinopathy, had more symptoms of neuropathy and peripheral vascular disease, had seen an ophthalmologist within 2 yr, or monitored their blood glucose more often. In addition, younger-onset diabetic subjects with poorer visual acuity or who were on a combination insulin regimen and older-onset people taking insulin, having more education, or who were younger were more likely to recall they had retinopathy. Factors not associated with recall in either group included sex, duration of diabetes, proteinuria, glycosylated hemoglobin, and family income.

Conclusions

These results underscore the need to develop better methods to deliver health-care information to people who have diabetes.
Split-Mixed Insulin Regimen With Human Ultralente Before Supper and NPH (Isophane) Before Breakfast in Children and Adolescents With IDDM
Authors: Wolfsdorf Joseph I , Laffel Lori MB , Pasquarello Cynthia , Vernon Anne , Herskowitz Raymonde D
Published: March 2007

Objective

Fasting hyperglycemia is common in patients with insulin-dependent diabetes mellitus (IDDM) treated with twice-daily subcutaneous insulin regimens. We postulated that substituting human ultralente insulin for the presupper dose of intermediate-acting insulin would improve overnight glycemic control in children and adolescents with IDDM.

Research Design and Methods

This 6-mo double-blind crossover study compared a conventional insulin regimen, a mixture of human NPH and regular given before both breakfast and supper (NPH), with a novel twice-daily regimen in which human ultralente replaced NPH before the evening meal (ultralente). This study was comprised of 20 children and adolescents (mean age and duration of IDDM 11.3 ± 2.9 and 2.4 ± 1.3 yr, respectively) from the Youth Clinic of the Joslin Diabetes Center, all of whom regularly performed self-monitoring of blood glucose (SMBG) and had been treated exclusively with human insulin (mean daily dose 0.75 ± 0.22 U/kg). Subjects performed SMBG on a prescribed schedule with a glucose meter with an electronic memory, and recorded results of blood glucose measurements, insulin dosages, and episodes of hypoglycemia. Monthly measurements were obtained for height, weight, and HbA1, and mean daily insulin dosages and average blood glucose level before breakfast, lunch, supper, bedtime snack, and between 0200 and 0300 were calculated. Nonfasting serum lipids were measured at entry, crossover, and the end of the study.

Results

After 3 mo, mean HbA, did not differ significantly (9.1 ± 1.7 vs. 9.5 ± 1.4%, NPH and ultralente, respectively). Mean fasting blood glucose was significantly lower on ultralente (9.6 ± 1.9 vs. 10.3 ± 2.2 mM, P < 0.05, and blood glucose showed a similar trend (0.05 < P < 0.1) before lunch (8.9 ± 1.7 vs. 9.8 ± 2.6 mM. Mean blood glucose before bedtime snack was significantly lower (P < 0.01) on NPH (8.4 ± 1.9 vs. 10.0 ± 2.1 mM) but did not differ significantly before supper or between 0200 and 0300. On the two regimens, growth and serum lipids were normal and similar, and no differences were observed in the incidence or severity of hypoglycemia.

Conclusions

Compared with a mixed dose of regular and NPH, a similar dose of a mixture of regular and human ultralente insulin before supper caused a modest reduction in fasting blood glucose levels but was associated with higher blood glucose levels before the bedtime snack. Overall glycemic control, reflected in HbA1 values, was not significantly improved.
Elevated Cholesteryl Ester Transfer Protein Activity in IDDM Men Who Smoke: Possible Factor for Unfavorable Lipoprotein Profile
Authors: Dullaart Robin P F , Groener Johanna E M , Dikkeschei Bert D , Erkelens D Willem , Doorenbos Hieronymus
Published: March 2007

Objectives

To determine the effect of cigarette smoking on the activity of cholesteryl ester transfer protein (CETP) and high-density (HDL), low-density (LDL), and very-low-density (VLDL) lipoproteins in insulindependent diabetic (IDDM) men with microvascular complications.

Research Design and Methods

We perfomed a case-control study in a referral-based diabetes clinic on a sequential sample of 9 cigarettesmoking and 12 nonsmoking IDDM men with microvascular complications and 12 nonsmoking control men. CETP activity was determined in each serum with an isotope assay with exogenous cholesteryl esterlabeled LDL and HDL. The method is independent of the endogenous lipoprotein present in serum.

Results

The HDL-cholesterol (VLDL and LDL) ratio was lower in the smoking diabetic men than in the other groups (P < 0.05 vs. the nonsmoking diabetic men and P <0.01 vs. the control subjects). CETP activity was 70% higher in the smoking diabetic men than in the control subjects (P <0.01) and 30% higher than in the nonsmoking diabetic men (P <0.05). The HDL-cholesterol (VLDL and LDL) ratio and the apolipoprotein A-l-B ratio were inversely correlated to CETP activity in the diabetic patients (r = −0.52, P <0.02 and r = −0.45, P <0.05, respectively).

Conclusions

CETP activity is increased in cigarette-smoking IDDM men with microvascular complications. High CETP activity may contribute to the unfavorable lipoprotein profile in these patients.
Epidemiology of childhood IDDM in U.S. Virgin Islands from 1979 to 1988: Evidence of an Epidemic in Early 1980s and Variation by Degree of Racial Admixture
Authors: Tull Eugene S , Roseman Jeffrey M , Christian Cora L E
Published: March 2007

Objective

The epidemiology of insulin-dependent diabetes mellitus (IDDM) was evaluated in a predominantly black population in the U.S. Virgin Islands.

Research Design and Methodsd

Primary ascertainment of diabetic subjects was by retrospective review of hospital and clinic records, and IDDM was defined by Diabetes Epidemiology Research International Group criteria.

Results

For the period 1979–1988, 28 children < 15 yr of age were diagnosed with IDDM resulting in an average annual IDDM incidence rate (IR) of 7.5∕100,000 (95% confidence interval 4.7–10.3). A significant increase in IDDM incidence (P < 0.01) was observed when the IR rose to 28.4∕100,000 in 1984. White children had the highest IR (28.9∕100,000). The IR for Hispanics (7.2∕100,000) was slightly higher than that for blacks (5.9∕100,000). Among black children, a slight but nonsignificant male excess in incidence was observed (male-female ratio 1.5). When black or Hispanic patients were compared with age-matched control subjects with respect to grandparental race, the diabetic subjects had a greater percentage of white ancestry (P < 0.02 and P < 0.05, respectively). The incidence of IDDM in Caribbean blacks (West Indians) in the U.S. Virgin Islands was similar to blacks in the U.S.

Conclusions

The epidemic of IDDM in 1984 provides support for a possible pandemic in the early 1980s.
Prevalence of Diabetes in Mexican Americans, Cubans, and Puerto Ricans From the Hispanic Health and Nutrition Examination Survey, 1982–1984
Authors: Flegal Katherine M , Ezzati Trena M , Harris Maureen I , Haynes Maureen G , Juarez Rumaldo Z , Knowler William C , Perez-Stable Eliseo J , Stern Michael P
Published: March 2007

The purpose of this study was to estimate the prevalence of diagnosed and undiagnosed diabetes among Mexican Americans, Cubans, and Puerto Ricans in the United States and compare these estimates to data from prior surveys for U.S. non-Hispanic whites and blacks. Data for this study are from the Hispanic Health and Nutrition Examination Survey, a multipurpose cross-sectional survey of three U.S. Hispanic populations conducted in 1982–1984. The interviewed sample of people aged 20–74 yr included 3935 Mexican Americans in the southwest, 1134 Cubans in Florida, and 1519 Puerto Ricans in the New York City area. The diabetes component consisted of interview questions on diabetes diagnosis and treatment and an oral glucose tolerance test administered to a subsample. The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976–1980. In Cubans, the prevalence was similar to that for non-Hispanic whites. In men and women 45–74 yr of age, the prevalence of diabetes was extremely high for both Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%) or non-Hispanic whites (12%). The total prevalence of diabetes was not significantly different for Mexican Americans and Puerto Ricans but was significantly lower for Cubans. The relatively lower prevalence of diabetes among Cubans and the high prevalence in both Mexican Americans and Puerto Ricans may be related to socioeconomic, genetic, behavioral, or environmental factors.
Microvascular Complications of NIDDM in Hispanics and Non-Hispanic Whites: San Luis Valley Diabetes Study
Authors: Hamman Richard F , Franklin Gary A , Mayer Elizabeth J , Marshall Sally M , Marshall Julie A , Baxter Judith , Kahn Louise B
Published: March 2007

The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case-control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20–74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4–63.7) than in Hispanics (41.8 per 100, 95% CI 34.8–48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people.
Does Insulin Species Modify Counterregulatory Hormone Response to Hypoglycemia?
Authors: Jones Timothy W , Caprio Sonia , Diamond Michael P , Hallarman Lynn , Boulware Susan D , Sherwin Robert S , Tamborlane William V
Published: March 2007

Objective

To examine whether pork and human insulin induce different counterregulatory responses to hypoglycemia.

Research Design and Methods

The responses to a mild hypoglycemic stimulus were determined in 35 healthy young adults with the glucose-clamp technique to ensure standardization of glucose and insulin levels. Either pork (n = 15) or human (n = 20) regular insulin was infused (0.8 mU·kg−1·min−1) to lower plasma glucose from 4.7 ± 0.07 to 3.3 ± 0.04 mM (both groups) over ∼ 40 min. Plasma glucose was maintained at that level (with variable rate glucose infusion) for an additional 60 min.

Results

Steady-state insulin levels were similar in both groups (316 ± 50 vs. 280 ± 29 pM, pork vs. human). Before insulin administration, basal counterregulatory hormone levels were indistinguishable. Most importantly, after plasma glucose was lowered, hormonal responses were nearly identical. No significant differences in peak values of epinephrine (1769 ± 404 vs. 1775 ± 311 pM, pork vs. human), norepinephrine (1.64 ± 0.23 vs. 1.87 ± 0.20 nM, pork vs. human), glucagon (163 ± 29 vs. 175 ± 20 ng/L, pork vs. human), growth hormone (14 ± 3 vs. 17 ± 3 μ/L, pork vs. human), or cortisol (543 ± 83 vs. 458 ± 28 nM, pork vs. human) occurred.

Conclusions

Our data suggest that pork and human insulin produce a comparable and robust hormonal response in healthy adults under conditions of controlled hypoglycemia.
Lipid Status After Pancreas-Kidney Transplantation
Authors: Larsen Jennifer L , Stratta Robert J , Ozaki Claire F , Taylor Rodney J , Miller Suzanne A , Duckworth W C
Published: March 2007

Objective

–This study was performed to determine the net effects of euglycemia, resolution of renal failure, immunosuppressant drugs, and hyperinsulinemia on fasting lipid profiles of patients with renal failure and insulin-dependent diabetes mellitus (IDDM) after combined pancreas-kidney transplantation (PKT).

Research Design and Methods

–Thirty subjects with IDDM received PKT between April 1989 and October 1990, and all were studied. Mean ± SE age was 35.2 ± 1.3 yr; 19 recipients were men, and 11 were women. All had a functioning pancreatic allograft post-PKT. Fasting lipid profiles including total cholesterol (C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-chol), and C/HDL-chol were compared before and after PKT (38–555 days divided into groups: preoperation and 0–2, 3–8, and 9–19 mo).

Results

–Significant hyperlipidemia was observed preoperatively (means ± SE): C, 5.92 ± 0.27 mM; HDL-chol, 1.07 ± 0.09 mM; TG, 5.85 ± 0.56 mM; and C/HDL-chol, 6.49 ± 0.83. All lipids and C/HDL-chol dropped immediately after PKT (0-2 mo vs. preoperation, all P < 0.01, except HDL-chol). After this immediate postoperative period, C, HDL-chol, and TG stabilized at new concentrations. C (5.44 ± 0.22 mM) and TG (4.54 ± 0.48 mM) levels were < preoperation (not statistically significant and P < 0.05, respectively). HDL-chol was greater than preoperative values (1.29 ± 0.06 mM, P < 0.05). C/HDL-chol dropped after PKT (0-2 mo, 4.85 ± 0.18, P < 0.01) and continued to decrease throughout the observation period (3-8 mo, 4.42 ± 0.23; 9-19 mo, 4.23 ± 0.23; both P < 0.01 vs. preoperation). There was no statistical difference between lipid concentrations in male and female subjects.

Conclusions

–The lipid status of subjects with IDDM and renal failure was abnormal before PKT and once lipid concentrations stabilized after PKT (> 2 mo), HDL-chol was higher and TG and C/HDL-chol levels were significantly lower than preoperative values. If these changes are sustained, risk of future cardiovascular disease in this group of patients might be significantly reduced.
Topical Capsaicin in Painful Diabetic Neuropathy: Controlled Study With Long-Term Follow-Up
Authors: Tandan Rup , Lewis Gloria A , Krusinski Patricia B , Badger Gary B , Fries Timothy J
Published: March 2007

Objective

–We conducted an 8-wk controlled study with topical 0.075% capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy. Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal, chemical, and mechanical stimuli when applied topically.

Research Design and Methods

In 22 randomly assigned subjects, either capsaicin or vehicle cream was applied to painful areas 4 times/day. Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk.

Results

–Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status, as measured by physician's global evaluation (P = 0.038) and by a categorical pain severity scale (P = 0.057). Decrease in mean pain intensity by a visual analogue scale was 16% in capsaicin-treated and 4.1' in vehicle-treated subjects. Mean pain relief on visual analogue scale was 44.6 and 23.2', respectively. In a follow-up open-label study, – 50' of subjects reported improved pain control or were cured, and 25' each were unchanged or worse. A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time.

Conclusions

–Results from this preliminary study suggest that topical 0.075' capsaicin may be of value in subjects with diabetic neuropathy and intractable pain.
Lack of Effects of Hypoglycemia on Glucose Absorption in Healthy Men
Authors: Møller Jens , Laker Michael F , Gillespie Susan M , Ovesen Per G , Abildgaard Niels , Tian Rong , Jørgensen Jens O , Møller Niels
Published: March 2007

OBJECTIVE

To assess the effects of hypoglycemia on glucose absorption by examining the systemic appearance of 3-OMG (a glucose analogue that is transported by the same mechanism as glucose) after oral administration.

RESEARCH DESIGN AND METHODS

Six healthy males 22–31 yr of age were studied during a hypoglycemic (50 mg [2.7 mM]/100 ml) and a euglycemic (90 mg [5.0 mM]/100 ml) glucose clamp. At 50 min after exposure to insulin, an oral glucose load containing 20 g of glucose and 4.5 g of 3-OMG dissolved in 300 ml of tap water was administered. Insulin administration was interrupted 30 min after oral glucose administration.

RESULTS

Plasma glucose was clamped at 88 ± 1.3 mg (4.9 ± 0.1 mM)/100 ml during euglycemia and at 50 ± 1.9 mg (2.7 ± 0.1 mM)/100 ml during hypoglycemia. Concentrations of glucagon, growth hormone, cortisol, and epinephrine were significantly elevated during hypoglycemia. After 60 min, circulating 3-OMG concentrations increased to zeniths of 11.4 ± 0.2 mg (585 ± 10.0 mM)/100 ml (hypoglycemia) and 11.6 ± 1.1 mg (585 ± 56.0 μM)/100 ml (euglycemia; P = 0.95). Absorption of 3-OMG was evident between 15 and 20 min after administrations in both situations. Serum insulin was significantly lower during hypoglycemia compared with the control situation (345 ± 50 microM [hypoglycemia], 445 ± 50 μM [euglycemia], P = 0.03).

CONCLUSIONS

We conclude that hypoglycemia does not seem to affect intestinal absorption of glucose as judged by systemic appearance of 3-OMG.
Clinical Characteristics of IDDM in Hispanics and Non-Hispanic Whites: Little evidence of heterogeneity by ethnicity
Authors: Kostraba Jill N , Cruickshanks Karen J , Neville Terri G , Lawler-Heavner Janet , Chase H Peter , Klingensmith Georgeanna J , Gay Elizabeth C , Hamman Richard F
Published: March 2007

OBJECTIVE

To compare the clinical characteristics of IDDM in HD and NHWD subjects in order to evaluate potential heterogeneity of IDDM by ethnicity.

RESEARCH DESIGN AND METHODS

HD subjects (n = 73) and NHWD subjects (n = 97) were recruited from the Colorado IDDM Registry. The registry included individuals who were Colorado residents, < 18 yr old at diagnosis, placed on insulin within 2 wk of diagnosis, and had diabetes not secondary to other conditions. Residual β-cell function was measured as the 1-h C-peptide response to a Sustacal challenge.

RESULTS

HD subjects were similar to NHWD subjects in insulin dose, HbA1, HLA-DR antigens, ICAs, and family history of IDDM. HD subjects were more likely to have a family history of NIDDM than NHWD subjects (11 vs. 3%, P = 0.03). HD girls had higher C-peptide levels (0.27 vs. 0.11 nm/L [0.83 vs. 0.33 ng/ml], P = 0.01), BMI (22.7 vs. 20.9 kg/m2 P = 0.04), subscapular skinfold thickness (18.9 vs. 15.0 mm, P = 0.04), and WHR (0.81 vs. 0.77, P = 0.03) than NHWD females. After controlling for diabetes duration, BMI, sex, and family history of NIDDM, residual β-cell function was associated significantly with Hispanic ethnicity, although the term accounted for just 3% of the overall variability in C-peptide levels.

CONCLUSIONS

Little evidence of heterogeneity by ethnicity of IDDM patients in the Colorado IDDM Registry was found. Ethnic differences in C-peptide levels may be related to differences in body fat distribution in females rather than heterogeneity of the disease.
Prevalence of Corynebacteria in Diabetic Foot Infections
Authors: Bessman Alice N , Geiger Paul J , Canawati Hanna
Published: March 2007

OBJECTIVE

Microbiological flora of diabetic foot infections are usually polymicrobial and frequently include bacteria of the Corynebacterium sp. (diphtheroids). The purpose of this study was to determine the prevalence of these bacteria in both deep and superficial cultures in diabetic patients with foot infections.

RESEARCH DESIGN AND METHODS

The charts of 50 patients of successive admissions to the Orthopedic-Diabetes Service at our hospital were reviewed to obtain the following data: age, sex, ethnic origin, method of treatment of diabetes, blood glucose level, prior antibiotics, and reports of cultures taken from bedside and intraoperative sites. Data were analyzed to compare the prevalence of diphtheroids in reliable versus nonreliable cultures and the influence of other parameters on the presence of these organisms.

RESULTS

Fourteen of 19 (74%) of the intraoperative specimens grew diphtheroids compared with 25 of 65 (39%) of the bedside cultures, a highly significant difference. In addition, there was a somewhat greater occurrence of diphtheroids in women compared with men. The likelihood that contamination is the cause for the presence of diphtheroids is highly unlikely, because one arm of the study included cultures derived from deep tissue at the time of the surgical procedure (i.e., the intraoperative cultures). Cultures always grew at least one other organism in addition to the diphtheroid.

CONCLUSIONS

Corynebacteria, commonly known as diphtheroids, are present as a part of the polymicrobial flora in a large percentage of diabetic patients with foot infections. Because the diphtheroids were identified in culture material taken in the operating room or at the time of incision and drainage in a higher percentage of patients than in specimens from superficial cultures, it is highly unlikely that they are contaminants.
Glycemic Control and Complications in Type II Diabetes: Design of a feasibility trial
Authors: Abraira Carlos , Emanuele Nicholas , Colwell John , Henderson William , Comstock John , Levin Seymour , Nuttall Frank , Sawin Clark ,   VA CS Group (CSDM)
Published: March 2007

OBJECTIVE

To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection.

RESEARCH DESIGN AND METHODS

This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40–69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 × 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven-field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria.

CONCLUSIONS

This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points.
Prediction of Infant Birth Weight by GDM Screening Tests: Importance of plasma triglyceride
Authors: Knopp Robert H , Magee M Scott , Walden Carolyn E , Bonet Bartolome , Benedetti Thomas J
Published: March 2007

OBJECTIVE

We measured plasma glucose, GHb, GPro, IRI and TG at 24–28-wk gestation to determine the extent of elevations in GDM and relationships to glucose intolerance and infant macrosomia.

RESEARCH DESIGN AND METHODS

Plasma samples were obtained 1 h after ingestion of 50 g glucose after an overnight fast in 521 randomly selected negative screenees, 264 positive screenees with GTT−, and 96 positive screenees with GTT+ (GDM).

RESULTS

Screening test values in GDM subjects exceeded the GTT− group, whose values exceeded those of negative screenees: glucose, 9.6*, 8.7*, 6.3 mM; GHb, 5.2*, 4.9*, 4.7%; GPro, 3.1*, 3.0*, 2.8%; IRI, 791*, 662*, 410 pM; and TG, 2.3*, 1.9, 1.9 mM, (*P < 0.005 vs. negative screenees). TG was the only test elevated in the GDM but not in the GTT− groups. Screening test values correlated with GTT values in the following order (strongest to weakest): glucose* > TG* > GHb* > IRI > GPro (*statistical significance). Plasma TG was the only screening test significantly associated with birth weight corrected for gestational age (birth-weight ratio) (r = 0.09–0.16) (P < 0.05 to < 0.01) and was of the same order as 1- and 2-h GTT associations with birth weight (r = 0.13 and 0.14, respectively) (P < 0.05 to < 0.01). Plots of TG/birth-weight ratio increased linearly to the 80–90th TG percentile in negative screenees and GTT− subjects. GDM subjects followed this trend but with more variation. Above the 90th percentile for TGs, birth-weight ratio trended lower, significantly so when the groups were combined (P < 0.05). In multivariate analysis, TG was associated with birth-weight ratio even when maternal prepregnancy weight and pregnancy weight gain associations with TG and birth-weight ratio were controlled (P < 0.019).

CONCLUSIONS

Of the five screening tests evaluated, all were elevated in GDM, but TG is the best discriminator of GDM from the GTT− group, and it is the only test significantly related to birth-weight ratio—and to glucose intolerance besides glucose itself. The TG association with birth weight is not explained fully by maternal weight. The results suggest that plasma TG may be a physiological contributor to infant birth weight. Further evaluation of plasma TG in GDM screening is justified, but GHb, GPro, and IRI appear to hold less promise.
Methodological Issues in Diabetes Research: Measuring adherence
Authors: Johnson Suzanne Bennett
Published: March 2007

The prevalence of nonadherence in IDDM and NIDDM populations and conceptual and methodological issues relevant to measuring diabetes regimen adherence are reviewed. The prevalence of nonadherence varies across the different components of the diabetes regimen, during the course of the disease, and across the patient's life span. Although prevalence rates might be expected to differ between IDDM and NIDDM populations, this rarely has been evaluated. Conceptual problems in defining and measuring adherence include: the absence of explicit adherence standards against which the patient's behavior can be compared; inadvertent noncompliance attributable to patient-provider miscommunication and patient knowledge/skill deficits; the behavioral complexity of the diabetes regimen; and the confounding of compliance with diabetes control. Methods for measuring adherence include: health status indicators, provider ratings, behavioral observations, permanent products, and patient self-reports, including behavior ratings, diaries, and 24-h recall interviews. A measurement method should be selected on the basis of reliability, validity, nonreactivity, sensitivity to the complexity of diabetes regimen behaviors, and measurement independence from the patient's health status. The timing of measurements should be based on the stability of adherence behaviors and temporal congruity with other measures of interest (e.g., indexes of metabolic control). Directions for future research and suggestions for clinical practice are provided.
Persistence of Glucose Metabolism After Exercise in Trained and Untrained Soleus Muscle
Authors: Bonen Arend , Tan Meng H , Megeney Lynn A , McDermott J C
Published: March 2007

We tested the hypothesis that increments in glucose metabolism in muscles from trained animals are caused by training adaptations in skeletal muscle and not by the residual effects of the last training session. The effects of a single bout of exercise on glucose metabolism (glycolysis and glycogenesis) were compared, against appropriate controls, in untrained (experiment 1) and trained (experiment 2) rat soleus muscles immediately (t = 0) and 3, 6, 24, 48, and 96 h after a standardized bout of exercise. [3H]Glucose incorporation into glycogen and glycolysis was measured in vitro in the absence and presence of insulin (0.1 and 10 nM). Experiment 1: A single bout of exercise provoked an increase in glycogenesis in the exercised, untrained muscles compared with the nonexercised, untrained muscles (0–96 h; P = 0.006). Glycolysis was not altered (0–96 h; P > 0.05). Experiment 2: In the exercised trained soleus, rates of glycolysis were > in the exercised, untrained soleus, at insulin concentrations of 0.1 nM (0–96 h; P = 0.005) and 10 nM (0–96 h; P = 0.01), but not in the absence of insulin (0–96 h; P > 0.05). No differences were observed in the rates of glycogenesis (0–96 h; P > 0.05). Therefore, acute exercise provokes increments in glycogenesis, whereas training increases glycolysis, in the presence of insulin, for some time after exercise. We speculate that insulin-dependent increments in glycolysis in trained muscles are a consequence of increased glucose transport caused by a greater pool of insulin-translocatable, intracellular glucose transporters.
Current Hypotheses for the Biochemical Basis of Diabetic Retinopathy
Authors: Mandarino Lawrence J
Published: March 2007

Diabetic retinopathy is one of the leading causes of vision loss in industrialized countries. Despite recent advances, the biochemical basis for the development of this diabetic complication is uncertain. Although retinal circulation is unique in that it is readily observable noninvasively, retinal tissue is extremely difficult to study in humans because of the problems inherent in obtaining fresh, appropriate biopsy material. Moreover, because of the difficulties in working with animal models of diabetic retinopathy, such as the dog, many investigators have turned to cell-culture models, especially those using primary cultures of retinal capillary endothelial cells and pericytes. Diabetic retinopathy involves both morphological and functional changes in the retinal capillaries. Morphological changes include basement membrane thickening and pericyte disappearance; functional changes include one important early change—increased permeability—which may be attributable to endothelial cell changes and basement membrane leakiness. Investigators have described major biochemical changes in cellular signaling pathways, including myo-inositol, inositol phosphates, and DAG metabolism, as well as decreased Na+-K+-ATPase and increased PKC activity. These defects may be related to the way endothelial cells and pericytes synthesize and interact with the extracellular matrix. Abnormalities in endothelial cell or pericyte interaction with the basement membrane may in turn lead to functional abnormalities, such as increased permeability.
Catecholamine Response During Human and Pork Insulin-Induced Hypoglycemia in IDDM Patients
Authors: Lingenfelser Thomas , Renn Walter , Plonz Christian , Radjaipour Mahmud , Eggstein Manfred , Jakober Bernhard
Published: March 2007

Objective

To evaluate the catecholamine response during human and pork insulin-induced hypoglycemia.

Research Design and Methods

Ten insulin-dependent diabetes mellitus (IDDM) patients without any signs of autonomic neuropathy received either human or pork insulin in a randomized crossover fashion on 2 nonconsecutive days. The glucose clamp technique was applied to achieve stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM.

Results

The effect of both types of insulin on glucose metabolism and circulating catecholamines was almost identical. There was a sharp rise of both epinephrine (P < 0.05) and norepinephrine (P < 0.02) during hypoglycemia,which did not depend on the type of insulin applicated. Symptom awareness increased significantly during the decrease of blood glucose concentration. Only during developing hypoglycemia (3.3-mM plateau), was this effect more pronounced (cumulative symptom score 2 vs. 26, P < 0.05) with pork insulin.

Conclusions

An attenuated catecholamine secretion seems not to be the putative mechanism of a reduced awareness of human insulin-induced hypoglycemia.