bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish Oil–Induced Changes in Apolipoproteins in IDDM Subjects
Authors: Mori Trevor A , Vandongen Robert , Masarei John RL
Published: March 2007

The aim of this study was to examine the effect of Max EPA (a commercially available fish oil preparation) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic (IDDM) men with dosages that were likely to be acceptable to patients. Twenty-two male IDDM patients aged 20–41 yr, 6 of whom had retinopathy, were recruited from the Royal Perth Hospital diabetic clinic. After screening, subjects were divided into three groups. Six of the subjects without retinopathy were randomly selected and allocated to a control group. The remaining 16 patients (10 without and 6 with retinopathy) received a fish oil supplement. All subjects were advised to maintain their usual dietary patterns. Sixteen patients, including the 6 with retinopathy, were instructed to take 15 Max EPA fish oil capsules/day with meals. Patients in the control group did not take Max EPA. Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol (P < 0.01), which could be accounted for by increases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. The increase in HDL cholesterol was explained by a 33% rise (P < 0.001) in its HDL2 subclass. Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-l increased after ingestion of fish oil and correlated significantly (P < 0.05) with the rise in HDL cholesterol. Apolipoprotein A-ll showed a significant fall at the end of Max EPA intake in a subgroup of patients with retinopathy, and this correlated significantly (P < 0.05) with the fall in HDL3 cholesterol observed at this time. A significant rise in apolipoprotein B (P < 0.05) was correlated with the rise in LDL cholesterol. Possible adverse effects of the increase in both total and LDL cholesterol after 15 g/day Max EPA may be compensated for by a rise in the protective HDL2 subclass. However, in view of this hypercholesterolemic effect and evidence that suggests that LDL apolipoprotein B may be a risk factor for coronary heart disease, these findings raise questions regarding the safety of fish oils in patients with IDDM.
Abnormal Lipoprotein Composition in Normolipidemic Diabetic Patients
Authors: Iwai Masahide , Yoshino Gen , Matsushita Masayuki , Morita Munetaka , Matsuba Kohji , Kazumi Tsutomu , Baba Shigeaki
Published: March 2007

To see whether there are any lipoprotein abnormalities in diabetic patients without hyperlipidemia, lipoprotein composition was examined in 75 strictly normolipidemic diabetic patients. Their plasma cholesterol (chol) and triglyceride (TG) were limited to <6.0 and <1.7 mM, respectively. Body-weight- and age-adjusted normolipidemic healthy subjects served as the control group. Plasma total chol and TG and low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol were identical in the diabetic and control subjects. Total apolipoprotein B (apoB) in the plasma of the diabetic subjects was significantly elevated. The chol-apoB ratio in the TG-rich (very-low-density + intermediate-density) lipoprotein fraction (Sf 12-400) of the diabetic subjects was significantly higher than the control value, whereas LDL-apoB levels were increased and chol-apoB ratio in the LDL fraction was significantly suppressed in the diabetic subjects. Because each LDL particle contains only one apoB molecule, apoB and chol-apoB ratio in this fraction can represent particle number and chol loading of the LDL particles, respectively. Thus, these data suggest that LDL particle number is increased, and the particles are chol depleted in diabetic subjects even if they are normolipidemic.
Insulin Administration via Liposomes
Authors: Spangler Ronald S
Published: March 2007

Liposomes have been used in insulin therapy as a means to selectively target insulin to the liver, enhance oral absorption of insulin, and prolong insulin action. Liposomes are an effective means of delivering insulin specifically to hepatocytes. The usefulness of hepatically targeted liposomes in the treatment of diabetes is restricted due to the requirement that they be given intravenously, the dilute concentration of insulin present in liposomal preparations, and the cost associated with liposome production. Encapsulating insulin in liposomes results in enhanced oral absorption of insulin. The high doses of liposome-entrapped insulin required perorally, coupled with extreme variability in the glycemic response to peroral liposomes, limits the value of peroral liposomal insulin as a viable diabetic therapy. Insulin action can be sustained via encapsulation of insulin in liposomes given subcutaneously. Most insulin appears to remain at the injection site, and the presence of a lipid matrix for subcutaneous insulin delivery raises concerns over enhanced antigenicity of liposomal insulin given subcutaneously. Viewed in the light of the limitations outlined above, the contribution of liposomal insulin to understanding and treatment of diabetes mellitus will probably be via use of hepatically targeted liposomes as a pharmacological probe to decipher the role of the liver in the metabolic complications associated with diabetes mellitus.
Care of Diabetic Patients by Optometrists in New York State
Authors: Olsen Carolyn L , Gerber Todd M , Kassoff Aaron
Published: March 2007

Objective

This study was undertaken to learn about the involvement of optometrists in the eye care of diabetic patients in New York and to collect baseline data for planning intervention programs in diabetic eye disease.

Research Design and Methods

This study was conducted by a mail survey being sent to all optometrists in New York whom we could identify through state sources (n = 2270). Three follow-up mailings were conducted.

Results

Eighty-six percent who received our mailing responded, 87%of whom reported that they see diabetic patients. Analysis was confined to this 87%. Routine retinal examinations were provided by 68% of the respondents who see diabetic patients, 62% of whom dilate the pupils. Sixty-eight percent who see diabetic patients diagnose retinopathy solely by their own examination, and 60% of these dilate. Follow-up of retinopathy was provided by 15% of optometrists who see diabetic patients, 90% of whom dilate the pupils of their diabetic patients. Twenty-five percent of respondents who see diabetic patients refer them to an ophthalmologist for diagnosis of retinopathy, and 67% refer all retinopathy patients to an ophthalmologist for follow-up. Although 91% of respondents recommended eye examinations at least annually for diabetic patients, only 68% specifically recommended annual examinations through dilated pupils. Those who dilate were significantly more likely to recommend annual dilated examinations than those who do not dilate, regardless of practice setting.

Conclusions

These findings indicate that optometrists as a group see many diabetic patients. Intervention strategies should include increased emphasis on the use of dilation when examining diabetic patients and annual dilated retinal examinations.
Major Cross-Country Differences in Risk of Dying for People With IDDM
Authors:   Diabetes Epidemiology Research International Mortality Study Group
Published: March 2007

Objective

Little is known concerning global differences in the risk of premature death for individuals developing youth-onset insulin-dependent diabetes mellitus (IDDM). The Diabetes Epidemiology Research International Study was developed to examine the mortality patterns of four population-based cohorts of IDDM cases from Allegheny County, Pennsylvania (n = 1000), Finland (n = 5146), Israel (n = 681), and Japan (n = 1428).

Research Design and Methods

All subjects were diagnosed as having diabetes, were <18 yr old at onset, were taking insulin at the time of hospital discharge, and were diagnosed between 1 January 1965 and 31 December 1979. The living status as of 1 January 1985 was determined.

Results

Overall, there were 182 deaths. Life-table analysis revealed that at 20-yr duration of diabetes, 5.5% of the cohort had died in Allegheny County in contrast to only 3.1% in Finland and 4.6% in Israel (P < 0.01). Follow-up for an additional 3 yr in the United States and Finland revealed major differences in the 30- to 39-yr age-group, with 3.9 times greater premature mortality in the U.S. cohort compared with the Finnish group (overall mortality 2.3 vs. 0.6%, respectively). The Japanese cohort was developed in a somewhat different manner than the other three; therefore, the populations of the U.S., Finland, and Israel were reconfigured to make them directly comparable to that of Japan. The Japanese cohort exhibited markedly higher age-adjusted mortality rates (n/100,000 person-yr of diabetes) than the other three (Japan 681, U.S. 230, Finland 171, and Israel 131).

Conclusions

These data indicate that young adult IDDM subjects are at an increased risk of premature death, there are differences in the mortality risk across countries, and both the U.S. and Japan have the major problem of an apparently excessive premature death rate among young people who have diabetes.
Effect of Motilin on Gastric Emptying in Patients With Diabetic Gastroparesis
Authors: Schmid Roland , Schusdziarra Volker , Allescher Hans-Dieter , Bofilias Ioannes , Buttermann Gerhard , Classen Meinhard
Published: March 2007

Oobjectives

Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances.

Research Design and Methods

The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects.

Results

During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values.

Conclusions

These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects.
Clinical Evaluation of Decision Support System for Insulin-Dose Adjustment in IDDM
Authors: Peters Achim , Rübsamen Markus , Jacob Ulrich , Look Dieter , Scriba Peter C
Published: March 2007

Objective

We developed a wallet-sized learning memory decision support system that helps patients with insulin-dependent diabetes mellitus adjust their insulin dosages.

Research Design and Methods

To determine the efficacy of the support system, we designed a randomized clinical trial with patients participating in a program in a diabetes education center. Patients were assigned to two groups of 21 patients each. All patients performed self-monitoring of blood glucose (SMBG) and were treated with multiple daily injections of insulin. Each of the patients was examined over a 32-day period. The basic educational program, i.e., practical advice in SMBG, diet, and exercise under homelike conditions, was identical in both groups. The only difference was that the first group used the computer for adjusting the insulin dose, whereas the second group received recommendations from the education team.

Results

The baseline HbA1 levels (9.8 ± 1.6 vs. 9.9 ± 1.6%) of both groups did not differ significantly. Mean blood glucose over the last 2 wk of the study was higher (P < 0.01) in the second group (8.4 ± 1.4 vs. 9.2 ± 2.0 mM); the frequencies of hypoglycemic episodes were not different (1.7 vs. 2.3%).

Conclusions

Metabolic control and safety were comparable in both groups. Thus, patients may benefit from such a system at home where no support by diabetes educators is available.
Insulin Sensitivity, Glucose Effectiveness, and Body Fat Distribution Pattern in Nondiabetic Offspring of Patients With NIDDM
Authors: Osei Kwame , Cottrell Daryl A , Orabella Martha M
Published: March 2007

Objective

To determine the relationship of insulin sensitivity (SI), glucose effectiveness (glucose-dependent glucose transport [SG]), and body fat distribution patterns in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM).

Research Design and Methods

Ten glucose-tolerant offspring of patients with NIDDM and 10 age-, sex-, and weight-matched healthy control subjects without family history of diabetes were studied with the minimal model method of Bergman et al. Body fat composition and distribution pattern were assessed by the bioelectrical impedance analyzer and waist-hip circumference ratios (WHR), respectively, in each subject.

Results

Mean fasting serum glucose (4.39 ± 0.17 vs. 3.94 ± 0.17 mM) and postglucose peak (18.50 ± 1.50 vs. 13.20 ± 1.06 mM) levels were significantly greater (P < 0.05) in the offspring than in the control subjects. Mean fasting serum insulin levels were slightly greater but not significantly different in the offspring versus control subjects (64 ± 14 vs. 29 ± 7 pM). After intravenous stimulation with glucose and tolbutamide, the mean serum insulin rose to significantly greater (P < 0.05) levels at t = 5 and 25 min in the offspring compared with the control subjects. Mean SI was significantly reduced by 45% in the offspring compared with the control subjects (4.77 ± 0.67 vs. 8.37 ± 1.24 × 10-4 min−1 · mU-1 · L-1;). However, SG was not different in the offspring versus control subjects (1.92 ± 0.12 vs. 2.10 ± 0.17 × 10-2 min−1). SI correlated significantly and inversely with the percentage of body fat mass (r = −0.580, P < 0.05) but not with the WHR (r = −0.019) in the offspring. We found a negative association between SI and basal serum insulin (r = −0.798, P < 0.01) but not with the poststimulation incremental insulin responses in the offspring. Family history of diabetes independently accounted for at least 27% of variance in the SI in our subjects.

Conclusions

Our study confirmed that insulin insensitivity but not a reduced glucose effectiveness exists in young glucose-tolerant offspring of patients with NIDDM. The reduced SI appears to be causally related to the total body fat content and may be a familial and/or genetic trait in the offspring.
Insulin Absorption, Glucose Homeostasis, and Lipolysis in IDDM During Mental Stress
Authors: Fernqvist-Forbes Eva , Linde Birgitta
Published: March 2007

Objective

To study the effects of mental stress on the absorption kinetics of insulin and on glucose homeostasis and lipolysis in insulin-dependent diabetes mellitus (IDDM).

Research Design and Methods

Nine IDDM patients were exposed to the Stroop color word conflict test (CWT) during 40 min after injection of 125I-labeled soluble human insulin (10 U) into the abdomen. Adipose tissue blood flow (133Xe-clearance) was determined concomitantly to elucidate the importance of blood flow for insulin absorption during CWT. The effect of the CWT was followed by measurement of arterial levels of catecholamines and as blood pressure and heart-rate responses. Lipolysis was measured as arterial glycerol levels, and ketone body levels were monitored by determination by β-hydroxybutyrate.

Results

Although insulin absorption (residual 125I-radioactivity and plasma free insulin levels) and the arterial levels of glucose and β-hydroxybutyrate were not significantly changed by the CWT, arterial glycerol and norepinephrine levels and adipose tissue blood flow were ~ doubled, and epinephrine levels increased fourfold. Heart rate increased ~ 35 beats/min and mean blood pressure ~ 25 mmHg.

Conclusions

The results suggest that intense mental stress of 40 min duration does not alter the absorption of subcutaneously injected insulin, glucose homeostasis, or ketone body levels in patients with IDDM, despite a considerable increase in blood flow and lipolysis.
Absorption Kinetics and Action Profiles of Subcutaneously Administered Insulin Analogues (AspB9GluB27, AspB10, AspB28) in Healthy Subjects
Authors: Kang Steven , Brange Jens , Burch Anna , Vølund Aage , Owens David R
Published: March 2007

Objective

The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated.

Research Design and Methods

Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol·kg−1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol·kg−1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations.

Results

The three analogues were absorbed 2–3 times faster than human insulin. The mean ± SE time to 50% residual radioactivity was 94 ± 6 min for AspB10 compared with 184 ± 10 min for human insulin (P < 0.001), 83 ± 8 min for AspB28 (P < 0.005), and 63 ± 9 min for AspB9GluB27 (P < 0.001) compared with 182 ± 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P < 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61–65 min postinjection compared with 201–210 min for the reference human insulins (P < 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P < 0.05) and AspB28 (P < 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P < 0.05).

Conclusions

The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.
Relationship Between Cows' Milk Consumption and Incidence of IDDM in Childhood
Authors: Dahl-Jørgensen Knut , Joner Geir , Hanssen Kristian F
Published: March 2007

Objective

To compare age-standardized incidence rates of diabetes in children 0–14 yr of age and cows' milk consumption in various countries.

Research Design and Methods

Ecological correlation study. Only incidence rates from diabetes registries carefully validated by the Diabetes Epidemiology Research International Study Group were used-Finland, Sweden, Norway, Great Britain, Denmark, United States, New Zealand, Netherlands, Canada, France, Israel, and Japan. Data on fluid cows' milk consumption in corresponding countries were obtained from the International Dairy Federation.

Results

Correlation between milk consumption and incidence of insulin-dependent diabetes mellitus (IDDM) was 0.96. The data fit a linear regression model, and analysis showed that 94% of the geographic variation in incidence might be explained by differences in milk consumption.

Conclusions

The results support the hypothesis that cows' milk may contain a triggering factor for the development of IDDM.
Subcutaneous Insulin Absorption Explained by Insulin's Physicochemical Properties: Evidence From Absorption Studies of Soluble Human Insulin and Insulin Analogues in Humans
Authors: Kang Steven , Brange Jens , Burch Anna , Vølund Aage , Owens David R
Published: March 2007

Objective

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans.

Research Design and Methods

Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external γ-counting.

Results

The mean ± SE initial fractional disappearance rates for the four preparations were 20.7 ± 1.9 (hexameric soluble human insulin), 44.4 ± 2.5 (dimeric analogue AspB10), 50.6 ± 3.9 (analogue AspB28), and 67.4 ± 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P < 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P < 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = −0.98, P < 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 ± 6.8; dimer 44.4 ± 2.5 from 0 to 2 h and 68.9 ± 3.5 from 2.5 h onward; and hexameric insulin 20.7 ± 1.9 from 0 to 2 h, 45.6 ± 5.0 from 2.5 to 5 h, and 70.6 ± 6.3 from 5 h onward.

Conclusions

Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.
Effect of Antecedent Glucose Control on Cerebral Function During Hypoglycemia
Authors: Amiel Stephanie A , Pottinger Richard C , Archibald Helen R , Chusney Gary , Cunnah David TF , Prior Pamela F , Gale Edwin AM
Published: March 2007

Objective

The incidence of both severe and asymptomatic hypoglycemia is increased threefold in intensively treated diabetic patients. To examine whether this reflects cerebral adaptation to low blood glucose levels, we investigated the effect of preceding glycemic experience on hormonal, EEG, and evoked potential responses to experimentally induced hypoglycemia with the slow-fall clamp.

Research Design and Methods

Three groups were examined: well-controlled diabetic patients and patients with insulinoma (group 1), poorly controlled diabetic patients (group 2), and nondiabetic subjects (group 3).

Results

The glucose threshold for epinephrine release was lower in group 1 (2.3 ± 0.1 vs. 3.0 ± 0.3 and 3.1 ± 0.1 mM, P < 0.02), and the peak epinephrine response was reduced (1.29 ± 0.36 vs. 5.48 ± 1 and 5.62 ± 1.2 nM, P < 0.01) compared with groups 2 and 3, whereas symptoms were not perceived until a lower blood glucose level had been reached (2.0 ± 0.2 vs. 3.3 ± 0.4 and 2.6 ± 0.2 mM, P < 0.01). Other counterregulatory responses were similarly delayed and diminished. In contrast, EEG changes that were compatible with hypoglycemia were detected in all subjects in group 1 (blood glucose 1.9 ± 0.1 mM) but in only two in group 2 and none in group 3, despite similar blood glucose nadirs.

Conclusions

The glycemic threshold for hormonal responses to hypoglycemia falls in individuals with intensively treated diabetes or insulinomas, but these patients are more likely to develop EEG abnormalities during hypoglycemia. This disparity helps explain the increased vulnerability of intensively treated patients to severe hypoglycemia.
Color Discrimination and Accuracy of Blood Glucose Self-Monitoring in Type I Diabetic Patients
Authors: Sawicki Peter T , Karschny Lothar , Stolpe Verena , Wolf Elmar , Berger Michael
Published: March 2007

Objective

To determine the importance of color discrimination ability regarding accuracy in the self-monitoring of blood glucose.

Research Design and Methods

Two hundred two insulin-dependent (type I) diabetic patients performed the Fansworth-Munsell 100-hue test and a second group of 159 type I diabetic patients performed a new Düsseldorf 26-hue test. Error scores in both tests were compared with error scores of patients' self-monitoring of blood glucose measurements with Chemstrip Haemoglucotest 20'800 strips.

Results

Color discrimination ability decreased with age, diabetes duration, and presence of retinopathy. It was independent of the degree of glycemia and accuracy of self-monitoring of blood glucose.

Conclusions

Impaired color vision by itself is no reason to abandon self-monitoring of blood glucose with visually read strips.
Autonomic Nervous Dysfunction in Essential Hypertension
Authors: Julius Stevo
Published: March 2007

Borderline hypertension, a condition in which the blood pressure oscillates between normal and high values, is a predictor of future more severe hypertension. Pathophysiologically, borderline hypertension is different from established hypertension. A large proportion of such patients have elevated cardiac output and a normal vascular resistance. In established hypertension, the output is normal and resistance is elevated. The elevation of cardiac output in borderline hypertension is neurogenic; it can be abolished by an autonomic blockade of the heart. In addition to an increased cardiac sympathetic drive, increased sympathetic tone to the kidney, arterioles, and veins has also been found. In parallel with the hypersympathetic state, patients with borderline hypertension also show decreased parasympathetic tone. The enhanced sympathetic tone leads to a decreased cardiac responsiveness, and eventually, the cardiac output returns to the normal range. High blood pressure causes vascular hypertrophy, and hypertrophic vessels are hyperresponsive to vasoconstriction. These secondary changes in the responsiveness of the heart and blood vessels are the basis of transition from a high cardiac output to high-resistance hypertension. These hemodynamic changes are associated with a downregulation of the sympathetic tone. A picture of an apparently nonneurogenic high-resistance hypertension emerges. Nevertheless, when assessed in regard to the enhanced pressor responsiveness, the sympathetic drive in such patients is still excessive. Despite the apparently normal tone, the sympathetic nervous system continues to play an important pathophysiological role in established hypertension. Borderline hypertension is associated with numerous metabolic abnormalities including obesity and insulin resistance. It is tempting to view all these abnormalities as a common expression of the increased sympathetic drive in hypertension. Explanation of the basis of the association of hypertension and metabolic abnormalities promises to bring new insights into the pathophysiology of two common diseases of civilization: hypertension and diabetes mellitus.
Abdominal Obesity and Physical Inactivity as Risk Factors for NIDDM and Impaired Glucose Tolerance in Indian, Creole, and Chinese Mauritians
Authors: Dowse Gary K , Zimmet Paul Z , Gareeboo Hassam , Alberti K George M M , Tuomilehto Jaakko , Finch Caroline F , Chitson Pierrot , Tulsidas Harish
Published: March 2007

Objective

We wanted to determine whether obesity, abdominal fat distribution, and physical inactivity act similarly and independently as risk factors for noninsulin- dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in Hindu and Muslim Asian Indians, African-origin Creoles, and Chinese Mauritians.

Research Design and Methods

We examined a population-based random cluster sample of 5080 adult subjects from the Indian Ocean island of Mauritius. Glucose tolerance was assessed with a 75-g oral glucose tolerance test and World Health Organization criteria.

Results

Univariate data and multiple logistic regression models indicated that age, family history of diabetes, body mass index (BMI), waisthip ratio (WHR), and physical inactivity conveyed similar risk for NIDDM (and IGT) in each ethnic group. After adjusting for all other factors, Hindu ethnicity conferred additional risk for NIDDM (but not IGT) in men, but in women there were no clear ethnic differences. Although BMI and WHR were independently significant risk factors, WHR conveyed relatively stronger risk for NIDDM than BMI in women, whereas the converse was true in men. For ethnic groups combined, the independent odds ratios for IGT associated with moderate and low physical activity scores (relative to high) were 1.56 and 1.71 (P < 0.05), respectively, in men and 1.32 and 1.69 (P < 0.05) in women. In subjects with asymptomatic NIDDM diagnosed during the survey, the independent odds ratios were 1.96 and 2.00 (P < 0.05) in men and 1.73 and 2.70 (P < 0.05) in women.

Conclusions

These data indicate that BMI, abdominally distributed fat, and physical inactivity are important independent risk factors for both IGT and NIDDM in diverse ethnic groups. Attributable risk fractions for Mauritius suggest that populationwide modification of levels of these risk factors could potentially result in substantially lower occurrence of NIDDM (and IGT). Such interventions should be attempted in high-risk populations.
Epidemiology and Prevention of Periodontal Disease in Individuals With Diabetes
Authors: Katz Patricia P , Wirthlin M Robert , Szpunar Susan M , Selby Joseph V , Sepe Stephen J , Showstack Jonathan A
Published: March 2007

Objective

This article reviews the epidemiological evidence of the relationship between diabetes and periodontal disease, possible physiological mechanisms for the association, and effects of interventions on the occurrence and severity of periodontal disease among individuals with diabetes.

Research Design And Methods

A comprehensive qualitative review of published literature in the area was performed.

Results

Much of the research in this area was found to contain methodological problems, such as failing to specify the type of diabetes, small sample sizes, and inadequate control of covariates such as age or duration of diabetes.

Conclusions

Trends indicate that periodontal disease is more prevalent and more severe among individuals with diabetes. This trend may be modified by factors such as oral hygiene, duration of diabetes, age, and degree of metabolic control of diabetes. Generally, poor oral hygiene, a long history of diabetes, greater age, and poor metabolic control are associated with more severe periodontal disease. The association of diabetes and periodontal disease may be due to numerous physiological phenomena found in diabetes, such as impaired resistance, vascular changes, altered oral microflora, and abnormal collagen metabolism. With some modifications, the same prevention and treatment procedures for periodontal disease recommended for the general population are appropriate for those with diabetes. People with diabetes who appear to be particularly susceptible to periodontal disease include those who do not maintain good oral hygiene or good metabolic control of their diabetes, those with diabetes of long duration or with other complications of diabetes, and teenagers and pregnant women.
Nonpharmacological Treatment of Hypertension in Diabetes Mellitus
Authors: Tjoa Hong I , Kaplan Norman M
Published: March 2007

Hypertension may be partially or completely controlled by appropriate use of nondrug therapies. Because diabetic patients are so often hypertensive and because the same nondrug therapies effective for treatment of hypertension may also benefit the diabetes, the use of nondrug therapies is particularly important in these patients. Evidence about the effectiveness of various nondrug therapies is provided along with practical suggestions to improve patient adherence to them.
Epidemiological Correlates of NIDDM in Hispanics, Whites, and Blacks in the u.s. Population
Authors: Harris Maureen I
Published: March 2007

Characteristics, prevalence, and risk factors for non-insulin-dependent diabetes mellitus (NIDDM) among Hispanics, blacks, and whites aged 20–74 yr in the United States population were investigated with two national surveys that used a household interview to ascertain diagnosed diabetes and a 75-g 2-h oral glucose tolerance test to measure undiagnosed diabetes. The Hispanic Health and Nutrition Examination Survey of 1982–1984 studied Mexican Americans in the southwest U.S., Cuban Americans in the Miami, Florida, area, and Puerto Ricans in the New York City area. The National Health and Nutrition Examination Survey of 1976–1980 examined a national sample of U.S. residents, of whom data on blacks and whites were analyzed. People with diagnosed diabetes in the five populations were similar with respect to mean age (53–57 yr), age at diagnosis (45–48 yr), duration of diabetes (6.9–8.7 yr), and diabetes therapies (58–67% using pharmacological treatment). Mean age of people with undiagnosed diabetes (51-59 yr) was comparable to that of diagnosed cases, and mean fasting (7.1–7.8 mM) and 2-h postchallenge plasma glucose (14.1–15.5 mM) values for people with undiagnosed diabetes were similar among the five populations. However, obesity levels varied by race, sex, and whether diabetes was diagnosed or undiagnosed. Age-standardized prevalence of diabetes (sum of diagnosed and undiagnosed cases) was 6.2% in whites, 9.3% in Cubans, 10.2% in blacks, 13% in Mexican Americans, and 13.4% in Puerto Ricans. Thus, compared to whites, diabetes rates were 50–60% higher among Cubans and blacks and 110–120% higher among Mexican Americans and Puerto Ricans. Age-standardized rates of impaired glucose tolerance were similar among the five populations (10.3–13.8%). Increasing age, obesity, and family history of diabetes were associated with higher rates of diabetes but sex, physical activity, education, income, and acculturation were not risk factors or were only weakly associated with diabetes prevalence.
Relationship Between First-Phase Insulin Secretion and Age, HLA, Islet Cell Antibody Status, and Development of Type I Diabetes in 220 Juvenile First-Degree Relatives of Diabetic Patients
Authors: Robert Jean-J , Deschamps Ingeborg , Chevenne Didier , Roger Marc , Mogenet Agnès , Boitard Christian
Published: March 2007

Objective

To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes.

Research Design and Methods

Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3–29 yr) of diabetic patients; 75 underwent two or more tests.

Results

At the first test, insulin responses correlated with age in ICA− children ≤ 11 yr old (r = 0.46, P < 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children < 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA− subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA− subjects displayed distinct changes; the mean ± SE insulin response increased in ICA− subjects from 619.2 ± 40.8 to 716.4 ± 50.4 pM (P < 0.001) but declined in ICA+ subjects from 403.2 ± 91.8 to 313.8 ± 67.2 pM (P < 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA− subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response.

Conclusions

Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.
Effects of Human Insulin on Insulin Binding Antibody Production in Nondiabetic Subjects
Authors: Davis Stephen N , Thompson Christopher J , Peak Matthew , Brown Mavis D , Alberti K George M M
Published: March 2007

Objective

—To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production.

Research Design and Methods

—Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone.

Results

—Mean ± SE basal insulin antibody levels (1.2 ± 0.2 μg/L) increased to a maximal level of 4.5 ± 0.8 μg/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 ± 0.3 μg/L. This represented a highly significant overall increase (P < 0.001). A control group of six insulin-dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 ± 0.7–2.7 ± 0.6 μg/L).

Conclusions

—These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy.
Standardization of IVGTT to Predict IDDM
Authors: Bingley Polly J , Colman Peter , Eisenbarth George S , Jackson Richard A , McCulloch David K , Riley William J , Gale Edwin A
Published: March 2007

OBJECTIVE

To review current practice in centers that use the IVGTT for prediction of IDDM. To establish consensus protocol for performance of the test.

RESEARCH DESIGN AND METHODS

Postal questionnaires were delivered to 12 centers.

RESULTS

Eleven centers used a glucose dose of 0.5 g/kg and 1 used 0.3 g/kg; the dosage in adults was limited to a maximum of 25–50 g in some centers but others applied no upper limit. The glucose concentration of the infusate varied between 20 and 66%. Eight centers injected glucose manually, two used a syringe pump, and two used gravity infusion. The period of infusion ranged from 30 ± 10 s to 4 ± 2 min, and time zero was taken as the start (1 center), middle (1 center), or end (10 centers) of the infusion. The potential range in timing of the + 1-min sample varied between 1 and 7 min from the start of the infusion. Quality-assurance standards for the insulin assays used were not always appropriate for the fasting and low stimulated range of insulin levels.

CONCLUSIONS

The first-phase insulin response to the IVGTT is widely measured as an index of risk of progression to IDDM. We established that methodology varies widely. Because of this, a new standard protocol for use in prediction of IDDM was agreed by an ICARUS working group and is described herein.
Residual Left Ventricular Pump Function After Acute Myocardial Infarction in NIDDM Patients
Authors: Iwasaka T , Takahashi N , Nakamura S , Sugiura T , Tarumi N , Kimura Y , Okubo N , Taniguchi H , Matsui Y , Inada M
Published: March 2007

OBJECTIVE

Left ventricular remodeling occurs immediately after MI, involving structural changes in noninfarcted segment. However, the residual left ventricular pump function in NIDDM patients after acute MI has not been clarified. The purpose of this study was to evaluate the difference in the process of left ventricular remodeling between NIDDM and nondiabetic patients.

RESEARCH DESIGN AND METHODS

Left ventricular regional EF images obtained by radionuclide angiography were investigated in 20 NIDDM and 29 nondiabetic patients the 3rd wk after acute MI.

RESULTS

Regional EF of the noninfarcted area and P/V had a significant hyperbolic relation with left ventricular EDV in both groups of patients. Despite no difference in the extent of myocardial necrosis and the number of coronary vessels diseased between NIDDM and nondiabetic patients, regional EF of the noninfarcted area and P/V were significantly lower when left ventricular EDV increased in NIDDM patients compared with nondiabetic patients.

CONCLUSIONS

Pathogenetic changes of the residual myocardium associated with NIDDM may adversely influence the process of left ventricular remodeling after MI, especially in patients with increased left ventricular EDV.
Mexiletine in the Treatment of Diabetic Neuropathy
Authors: Stracke Hilmar , Meyer Ulrike E , Schumacher Helmut E , Federlin Konrad
Published: March 2007

OBJECTIVE

To prove the efficacy of mexiletine in painful diabetic neuropathy.

RESEARCH DESIGN AND METHODS

Treatment was provided in three dosages. For pain measurements, a VAS and McGill's verbal rating scale were chosen. Ninety-five patients were included in the study.

RESULTS

A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo. The total evaluation (PRIT) of the McGill scale fell just below the level of significance. More specific exploratory evaluations of subclasses of the McGill scale, representing different degrees of pain, gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items. In special subgroups, which were formed according to types and courses of complaints compiled at the beginning of this evaluation, the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale.

CONCLUSIONS

Evidence strongly indicates that, in particular, those patients with stabbing or burning pain, heat sensations, or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg/day seems to be appropriate. With an increase in the antiarryhthmic dosage level, the efficacy does not rise proportionally. Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range, even < placebo; and remarkably, no cardiovascular side effects were noted. Further studies should avoid global assessments and pay more attention to the variety of complaints and quality of life.
Interaction of Insulin and Exercise on Glucose Transport in Muscle
Authors: Rodnick Kenneth J , Piper Robert C , Slot Jan W , James David E
Published: March 2007

Glucose transport is the rate-limiting step for glucose utilization in muscle. In muscle and adipose tissue, glucose transport is acutely regulated by such factors as insulin and exercise. Translocation of glucose transporters (GLUT4) from an intracellular domain to the cell surface is the major mechanism for this regulation. Using immunocytochemistry, the intracellular distribution of GLUT4 under resting conditions is similar in adipocytes and myocytes. GLUT4 is concentrated in tubulovesicular structures either in the trans-Golgi region or in the cytosol, often close to the cell surface but not on the cell surface. After stimulation, cell surface GLUT4 labeling is increased by as much as 40-fold.

GLUT4 is chronically regulated by altered gene expression. Neural and/or contractile activity regulates GLUT4 expression in muscle: 1) GLUT4 levels differ among muscles of different fiber type; 2) GLUT4 levels in muscle are increased with exercise training and decreased with denervation; and 3) cultured muscle cells, which lack an intact nerve supply, express very low levels of GLUT4. GLUT4 expression appears to be regulated in parallel with many oxidative enzymes in muscle, suggesting that there may be a unified developmental program that determines the overall metabolic properties of a particular muscle. Preliminary evidence suggests that impaired GLUT4 expression in muscle is not the primary defect associated with insulin resistance. Nevertheless, it is conceivable that the adaptive increase in muscle GLUT4 that is found with exercise training may have beneficial effects in insulin-resistant states such as non-insulin-dependent diabetes.
Metabolic Responses to Exercise: Effects of endurance training and implications for diabetes
Authors: Richter Erik A , Turcotte Lorraine , Hespel Peter , Kiens Bente
Published: March 2007

In this study, some important metabolic responses to exercise will be discussed, and aspects of particular interest for patients with diabetes mellitus will be emphasized. Alterations in the metabolic responses to exercise induced by physical endurance training and consequences of training for metabolism of plasma lipids and lipoproteins will be discussed. Glucoregulation during exercise is not perfect in normal subjects and is less so in patients with diabetes mellitus. For instance, during intense exercise, large increases in the plasma glucose concentration occur and a state of insulin resistance exists for a few hours after intense exercise. Even so, increased sensitivity to insulin is found the day after intense exercise and also shortly after more moderate intensity exercise, both in healthy subjects and in patients with diabetes mellitus. Increased sensitivity to insulin is also found after endurance training, whereas insulin sensitivity is decreased after inactivity. Exercise training increases the ability of muscle to take up and oxidize free fatty acids during exercise and also increases the activity of the enzyme lipoprotein lipase in muscle. The activity of lipoprotein lipase in muscle correlates with muscle insulin sensitivity. This might explain why insulin resistance is often associated with hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol.
Interaction of Exercise and Insulin in Type II Diabetes Mellitus
Authors: Wallberg-Henriksson Harriet
Published: March 2007

In skeletal muscle, at the level of glucose transport, insulin resistance appears to be a major alteration responsible for decreased glucose disposal rates in non-insulin-dependent (type II) diabetes mellitus. This study focuses on in vitro studies of the glucose transport process in human and rat skeletal muscle. Muscle strips from a group of lean type II diabetic patients demonstrated a 50% decrease in insulin responsiveness for glucose transport when compared with nondiabetic subjects. These findings indicate the presence of postreceptor defects in type II diabetic muscles. Furthermore, in an isolated muscle preparation, it could be demonstrated that epitrochlearis muscles from streptozocin-induced diabetic rats were not only resistant to insulin, but also to exercise-induced increase in glucose transport. However, both regular physical exercise and insulin therapy normalized the decreased capacity for glucose transport in the diabetic rat muscles. Therefore, it appears that regular physical exercise and, in some cases insulin therapy, would be advisable for type II diabetic patients with marked muscular insulin resistance to improve peripheral glucose disposal rates.