bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose-Dependent Effects of Glyburide on Insulin Secretion and Glucose Uptake in Humans
Authors: Groop Leif C , Barzilai Nir , Ratheiser Klaus , Luzi Livio , Wåhlin-Boll Elisabeth , Melander Arne , DeFronzo Ralph A
Published: March 2007

Objective

To examine the relationship between plasma glyburide concentrations (0, 50, 100, 200, 400, and 800 nM) and the insulin response and glucose metabolism during euglycemic (4.6 ± 0.1 mM) and hyperglycemic (11.6 ± 0.2 mM) conditions.

Research Design and Methods

Nine healthy subjects participated in the study. Steady-state plasma glyburide concentrations were achieved by primed continuous intravenous infusion of glyburide.

Results

During both euglycemia and hyperglycemia, glyburide enhanced insulin secretion and glucose disposal only to drug levels of 100–200 nM corresponding to an oral dose ≤ 10 mg.

Conclusions

The data suggest that glyburide (and probably other sulfonylureas), operates within a narrow range of plasma concentrations (50–200 nM), which can be achieved with very low doses of the drug. It remains to be shown whether the threshold of maximal effect also in clinical practice is achieved with lower sulfonylurea doses than that currently used.
Effects of Dietary Carbohydrate and Fat Intake on Glucose and Lipoprotein Metabolism in Individuals With Diabetes Mellitus
Authors: Hollenbeck Clarie B , Coulston Ann M
Published: March 2007

The dietary treatment of individuals with diabetes remains a controversial issue. The major emphasis in recent years has been on the reduction of total fat and saturated fat and replacement with complex carbohydrate. The rationale for this approach is based on the premise that such diets will reduce the risk of coronary artery disease (CAD) by reducing total and low-density lipoprotein cholesterol concentrations. In this article, we review the available data and conclude that there is little evidence to support the notion that low-fat high-carbohydrate diets per se lead to any reduction in the risk for CAD in individuals with diabetes. The only data indicating that low-fat high-carbohydrate diets lead to beneficial effects on carbohydrate and lipoprotein metabolism are confounded either by the lack of suitable experimental control, by the fact that diets also differed in the type of dietary fat and amount of dietary cholesterol, or were enormously enriched in dietary fiber. When these factors are taken into consideration, there appears to be little evidence in support of the view that substituting carbohydrate for fat in the diets of individuals with diabetes results in any measurable beneficial effect. Indeed, it could be argued that the most characteristic defects in carbohydrate and lipoprotein metabolism are exacerbated in response to low-fat high-carbohydrate diets. Alternatively, the data presented herein strongly suggest that diets containing conventional quantities of fat, in which saturated fat is replaced by unsaturated fat and dietary cholesterol reduced, would result in the desired reductions to total and low-density lipoprotein cholesterol concentrations without the adverse effects of increased postprandial glucose and insulin concentrations, increased fasting and postprandial total and very-low-density lipoprotein triglyceride concentrations, and decreased fasting high-density lipoprotein cholesterol concentrations.
Topical Capsaicin in Painful Diabetic Neuropathy: Effect on Sensory Function
Authors: Tandan Rup , Lewis Gloria A , Badger Gary B , Fries Timothy J
Published: March 2007

Objective

–To examine the effect of capsaicin on sensory function in painful diabetic neuropathy.

Research Design and Methods

–We examined the effects of topical 0.075% capsaicin cream on thermal and vibration thresholds in 22 subjects with painful diabetic neuropathy who participated in a double-blind vehicle-controlled therapeutic trial.

Results

–After 8 wk of use, there was no significant change in warm and vibration thresholds, but the cold threshold was significantly reduced by capsaicin and vehicle creams to an equal degree. In fewer subjects who used capsaicin cream in an open-label study, there was no significant effect on sensory thresholds after up to 32 wk of use.

Conclusions

–Although our results and those of others show no adverse effects of topical 0.075% capsaicin on human sensory function, even in subjects with preexisting neuropathic sensory impairment, the small number of subjects tested does not justify an inferential statement on safety. Further studies in more subjects are warranted to ensure the long-term safety of capsaicin for pain relief in humans.
Increasing Trend of Outpatient Management of Children With Newly Diagnosed IDDM: Colorado IDDM Registry, 1978–1988
Authors: Kostraba Jill N , Gay Elizabeth C , Rewers Marian , Chase H Peter , Klingensmith Georgeanne J , Hamman Richard F
Published: March 2007

Objective

–To examine the management of newly diagnosed insulin-dependent diabetes mellitus (IDDM) in Colorado over time and to determine the prevalence of outpatient care at IDDM diagnosis on a statewide basis.

Research Design and Methods

–The Colorado IDDM Registry was used to assess medical care at the diagnosis of IDDM in 1182 patients < 18 yr of age between 1978 and 1988.

Results

–Twenty-three percent of children with IDDM in Colorado reported never being hospitalized during the diagnosis period. Treatment of IDDM at diagnosis (outpatient vs. inpatient) did not differ by age, sex, or ethnicity/race. Patients living in rural counties were less likely to have been treated as outpatients at diagnosis than those living in urban counties. Physicians at specialized diabetes clinics (e.g., The Barbara Davis Center for Childhood Diabetes and The Childrens Hospital) were more likely to treat newly diagnosed children in an outpatient setting than physicians not affiliated with these clinics. The proportion of patients receiving only outpatient care at IDDM diagnosis increased from 6% in 1978 to 35% in 1988. This increase can be attributed to three factors: 1) an increase in the number of Colorado children diagnosed at The Barbara Davis Center, where outpatient care is strongly advocated; 2) a change in treatment practices at The Childrens Hospital away from routine hospitalization at onset; and 3) a steady increase in outpatient care for newly diagnosed diabetic children by physicians who were not affiliated with the aforementioned specialized diabetes clinics.

Conclusions

–The relatively new practice of outpatient care at diagnosis of IDDM increased between 1978 and 1988 in Colorado, in both specialized diabetes clinics and physicians' practices not affiliated with specialized clinics.
Physical Activity and Proliferative Retinopathy in People Diagnosed With Diabetes Before Age 30 Yr
Authors: Cruickshanks Karen J , Moss Scot E , Klein Ronald , Klein Barbara E
Published: March 2007

OBJECTIVE

To examine the relationships of past and current physical activity to the prevalence of PDR.

RESEARCH DESIGN AND METHODS

Individuals diagnosed with diabetes < 30 yr of age (n = 818), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984–1986. Stereoscopic fundus photographs were graded for presence of PDR. Physical activity was assessed by an interviewer-administered standardized questionnaire.

RESULTS

Women diagnosed with diabetes < 14 yr of age who reported a history of participation in team sports in high school or college were less likely to have PDR at examination (OR 0.46, 95% CI 0.23, 0.93). Those women who reported current strenuous activity levels were less likely to have PDR (OR 0.34, 95% CI 0.13, 0.87). There were no significant associations between past or current physical activity and PDR in men. Current levels of energy expenditure were not related to PDR in either sex.

CONCLUSIONS

Higher levels of physical activity may be associated with a reduced risk of having PDR in women. However, the lack of similar findings in men suggests that physical activity may be a relatively unimportant factor in the etiology of PDR.
Insulin Action in Black Americans With NIDDM
Authors: Banerji Mary Ann , Lebovitz Harold E
Published: March 2007

OBJECTIVE

To assess the influences that obesity and hyperglycemia have on insulin action in black NIDDM patients.

RESEARCH DESIGN AND METHODS

Thirty-nine subjects were studied who had normal GHb levels and/or FPG <6.4 mM and who had not taken pharmacological agents for 2–91 mo before the study. Insulin action was studied using the euglycemic insulin clamp with a d-[3-3H] glucose infusion. Degree of obesity was assessed with BMI. During carefully monitored follow-up, 9 patients relapsed into a hyperglycemic state, and insulin action was restudied after acute reregulation of their plasma glucose.

RESULTS

Insulin action was related to the degree of obesity at the extremes of BMI: 7 of 8 patients (87.5%) with a BMI <24.0 kg/m2 were insulin sensitive, and 8 of 9 patients (88.9%) with a BMI >28.5 kg/m2 were insulin resistant. In the midrange BMI (24.0–28.5 kg/m2), patients were equally likely to be insulin resistant or insulin sensitive. A plot of frequency versus glucose disposal in those patients was compatible with a bimodal distribution (P < 0.025): 12 of 22 patients were normally insulin sensitive (glucose disposal 6.1–9.4 mg.kg−1 · min−1), and 10 were insulin resistant (glucose disposal 2.4–4.8 mg.kg−1 · min−1). Analysis of this midrange BMI group showed that in the insulin-sensitive group, an inverse relationship existed between BMI and glucose disposal (r = −0.64, P < 0.05), whereas no such relationship was found in the insulin-resistant group. The clinical characteristics of the midrange BMI group indicated that fasting plasma insulin, total cholesterol, and triglycerides were higher; whereas BMI, age, and FPG were not different in the insulin-resistant compared with the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group was decreased, independent of obesity, whereas it was unchanged in the insulin-resistant group.

CONCLUSIONS

Insulin resistance exists in only ∼ 50% of black NIDDM patients. The relationship between obesity and insulin resistance is not a simple one. The data can be explained by one of two hypotheses: 1) insulin resistance in black NIDDM patients is an acquired defect related to the development of obesity and is modulated by hyperglycemia, or 2) NIDDM exists as two variants, one with primary insulin resistance and one with normal insulin sensitivity, and that insulin resistance causes central and/or generalized obesity.
Prevalence of Glucose Intolerance in Asian Indians: Urban-rural difference and significance of upper body adiposity
Authors: Ramachandran Ambady , Snehalatha Chamukuttan , Dharmaraj Daisy , Viswanathan Moopil
Published: March 2007

OBJECTIVE

To evaluate the prevalence of NIDDM and IGT in the urban and rural areas in southern India.

RESEARCH DESIGN AND METHODS

Two populations of the same ethnic background, but different socioeconomic background were chosen for this study. Nine-hundred urban people and 1038 rural subjects were studied. Fasting and 2-h post-glucose capillary blood samples after a 75 g oral glucose load (WHO criteria) were obtained in these randomly selected adults (≥ 20 yr of age).

RESULTS

Using the WHO criteria, the prevalence of NIDDM, adjusted to the age of the respective general population, was 8.2% in the urban and 2.4% in the rural populations. The prevalence was 8.4 and 7.9%, respectively, in urban men and women, and 2.6 and 1.6% in rural men and women. The age-adjusted prevalence of IGT was 8.7 and 7.8% in the urban and rural areas, respectively. The prevalence of IGT was 8.8% in urban men and 8.3% in women; the corresponding values for rural men and women were 8.7 and 6.4%. The prevalence of NIDDM increased with age, markedly so in the urban people. The urban-rural difference was significant for NIDDM (X2 = 29.4, P < 0.001) but not for IGT. In the urban population, 65% of the NIDDM patients were known cases, whereas in the rural area, the known cases accounted for only 24%. Bivariate analysis showed an association of BMI, STR, and WHR with prevalence of NIDDM plus IGT. In the multiple logistic regression analysis, age, BMI, STR, and WHR were associated significantly with glucose intolerance in the urban population, whereas only age was significant in the rural population. The best predictors of NIDDM were age, BMI, WHR, and urbanization.

CONCLUSIONS

The study showed a high prevalence of NIDDM in the urban southern Indian population. The prevalence of NIDDM in the same ethnic group in rural areas was significantly lower. The prevalence of IGT was similar in both populations. Upper body adiposity was a significant predictor of NIDDM in this population with low rates of obesity.
Eating disorders in adolescents with IDDM: A controlled study
Authors: Peveler Robert C , Fairburn Christopher G , Boller Irene , Dunger David
Published: March 2007

OBJECTIVE

To determine the prevalence of clinical eating disorders and lesser degrees of disturbed eating in adolescents with IDDM and a matched sample of nondiabetic control subjects.

RESEARCH DESIGN AND METHODS

A cross-sectional survey of eating habits and attitudes conducted in 76 adolescents with IDDM, and age- and sex-matched nondiabetic control subjects. Eating disorder features were assessed by standardized research interview adapted for use with patients with diabetes (EDE). Glycemic control was assessed by GHb assay.

RESULTS

Adolescent girls with IDDM were heavier than nondiabetic female control subjects and were dieting more intensively to control their shape and weight. However, clinical eating disorders were no more common among adolescent girls with IDDM than among nondiabetic control subjects. Nine percent of the IDDM girls met diagnostic criteria for an operational version of “Eating disorder not otherwise specified.” Fifteen percent had omitted or reduced their dose of insulin to influence their shape and weight. Eating disorder features and insulin misuse for shape and weight control were not found in IDDM or nondiabetic boys, and these two groups did not differ in their body weight.

CONCLUSIONS

Adolescent girls with IDDM are heavier than their nondiabetic counterparts and diet more intensively to control their shape and weight. Disordered eating habits and weight control behavior are common, but no more so in IDDM than in nondiabetic subjects. Insulin misuse for the purpose of shape and weight control is not restricted to subjects with a clinical eating disorder. Disordered eating is associated with impaired glycemic control.
Diabetes Is Not Caused by Cassava Toxicity: A study in a Tanzanian community
Authors: Swai A B M , Mclarty D G , Mtinangi B L , Tatala S , Kitange H M , Mlingi N , Rosling H , Howlett W P , Brubaker G R , Alberti K G M M
Published: March 2007

OBJECTIVE

To test the hypothesis that consumption of cassava with liberation of cyanide causes diabetes in malnourished individuals.

RESEARCH DESIGN AND METHODS

Glucose tolerance was assessed in two rural communities in Tanzania; in one (Nyambori), the main source of calories was cassava; and in the other (Uswaa), cassava was rarely eaten. Undernutrition was prevalent in both communities. The people of Nyambori were known to have high dietary cyanide exposure for many years from consumption of insufficiently processed cassava. Of the 1435 people in Nyambori ≥ 15 yr old, 1067 (74%) were surveyed, and 1429 of 1472 (97%) eligible subjects in Uswaa were surveyed. All had 75-g oral glucose tolerance tests and measurement of BMI. Plasma and urine thiocyanate and blood cyanide also were measured in some subjects.

RESULTS

Mean ± SD plasma and urine thiocyanate levels in Nyambori were 296 ± 190 and 497 ± 457 μM (n = 204), respectively, compared with 30 ± 37 and 9 ± 13 μM, respectively, in Uswaa (n = 92) (P < 0.001 for all differences). The mean blood cyanide level in Nyambori was elevated (1.4 [range 0.1–30.2] μM; n = 91). The prevalence of diabetes in the cassava village (Nyambori) was 0.5% compared with 0.9% in Uswaa (NS). The prevalence of IGT was similar in the two villages in the 15- to 34- and the 34- to 54-yr-old age-groups; but in those ≥ 55 yr old, IGT was higher in Nyambori (17.4 vs 7.2%, P = 0.029). Mean fasting and 2-h blood glucose levels were slightly higher in Nyambori village after adjusting for age, sex, and BMI (4.5 vs. 4.2 and 5.0 vs. 4.4 mM, respectively).

CONCLUSIONS

High dietary cyanide exposure was not found to have had a significant effect on the prevalence of diabetes in an undernourished population in Tanzania. Cassava consumption is thus highly unlikely to be a major etiological factor in so-called MRDM, at least in East Africa.
Identifying Diabetic Patients at High Risk for Lower-Extremity Amputation in a Primary Health Care Setting: A prospective evaluation of simple screening criteria
Authors: Rith-Najarian Stephen J , Stolusky Thomas , Gohdes Dorothy M
Published: March 2007

OBJECTIVE

To evaluate prospectively a risk categorization scheme for lower-extremity problems that incorporates the Semmes-Weinstein 5.07 monofilament and a simple exam to stratify patients who were followed in a primary-care setting into risk groups for plantar ulceration and lower-extremity amputation.

RESEARCH DESIGN AND METHODS

Patients with diabetes in a well-defined American-Indian population were stratified into four risk categories based on sensation status to the 5.07 monofilament, the presence of foot deformity, and a history of lower-extremity events (amputation or ulceration): category 0, sensate; category 1, insensate; category 2, insensate with deformity; and category 3, history of lower extremity events. Patients were followed prospectively for lower extremity events and changes in sensation status.

RESULTS

We gave screening exams to 358 (88%) of 406 individuals with diabetes in the community. The distribution of patients for risk categories 0, 1, 2, and 3 was 74.3, 8.4, 4.5, and 13%, respectively. Over a 32-mo follow-up period, 41 patients developed ulcerations, and incidence rates correlated positively with increasing risk category (P < 0.00001). All 14 amputations occurred in risk groups 2 and 3.

CONCLUSIONS

These data suggest that the risk categorization described here may have a role in identifying patients at risk for lower extremity events who are followed in a primary-care setting.
Hemophilus Influenza Infection of an Implantable Insulin-Pump Pocket
Authors: Levy Richard P , Borchelt Mark D , Kremer Richard M , Francis Stephen J , O'Connor Carol A
Published: March 2007

OBJECTIVE

To increase awareness of adverse events associated with the use of implantable insulin pumps.

RESEARCH DESIGN AND METHODS

A descriptive case report of a pump implant infection.

RESULTS

This is a case report of one implanted insulin pump-pocket infection among a series of 15 patients. After exposure to a child with a respiratory infection on PID 30, V.L.C. (the patient) developed a fulminant pump-pocket infection. H. influenza was recovered from it. Despite aggressive antibiotic therapy, the infection could not be controlled. Insulin delivery ceased, and the pump was explanted. The pump-pocket infection rapidly resolved with pump removal, permitting later reimplantation.

CONCLUSIONS

We have adopted the American Heart Association indications and antimicrobial prophylaxis regimens recommended for prevention of endocarditis in patients with prosthetic values for patients with implanted insulin pumps.
Epidemiology of Insulin-Using Commercial Motor Vehicle Drivers: Major variability of state licensing requirements in the U.S.
Authors: Gower Idamae F , Songer Thomas J , Hylton Harold , Thomas Neill L , Ekoe Jean-Marie , Lave Lester B , LaPorte Ronald E
Published: March 2007

OBJECTIVE

Licensing agencies in many areas, including the U.S., prohibit insulin-using individuals from driving CMVs or large trucks. This study examined the debate over the risks of licensing insulin-using individuals to drive CMVs as an occupation, and the variations in regulations of different states.

RESEARCH DESIGN AND METHODS

As part of an ongoing review of the regulations governing interstate commerce in the U.S., we surveyed all 50 states and Washington, D.C. to determine the regulations concerning intrastate driving. We received responses from 48 states and D.C., representing 95% of the U.S. population.

RESULTS

Only 9 states reported preventing insulin users from acquiring a CMV license, whereas 39 states and D.C. permitted licensing within state boundaries. Of the states allowing insulin users to drive, 26 placed special requirements on CMV licensing.

CONCLUSIONS

The results indicate that, despite a standardized U.S. federal law for driving across states, enormous variability exists in the policies for driving within states, ranging from no restrictions to a complete ban on CMV driving for insulin users.
Leukocyte Scanning With 111In Is Superior to Magnetic Resonance Imaging in Diagnosis of Clinically Unsuspected Osteomyelitis in Diabetic Foot Ulcers
Authors: Newman Lisa G , Waller John , Palestro Christopher J , Hermann George , Klein Michael J , Schwartz Myron , Harrington Elizabeth , Harrington Martin , Roman Sheila H , Stagnaro-Green Alex
Published: March 2007

OBJECTIVE

To compare the accuracies of MRI and leukocyte scanning in diagnosing clinically unsuspected osteomyelitis in diabetic foot ulcers.

RESEARCH DESIGN AND METHODS

A prospective study of 16 diabetic foot ulcers in 12 patients, including both ambulatory and hospitalized patients, was performed at a university medical center. Pedal images were obtained by leukocyte scanning with [111In]oxyquinoline and MRI. Definitive diagnosis of osteomyelitis then was determined by bone biopsy for culture and histology.

RESULTS

Biopsy-proven osteomyelitis was present in 7 (44%) of the 16 foot ulcers. The diagnosis was suspected clinically in 0%. Leukocyte scanning was 100% sensitive, whereas MRI was only 29% sensitive in diagnosing osteomyelitis in diabetic foot ulcers. Specificities were 67 and 78%, respectively. The positive and negative predictive values (70 and 100%, respectively) for the leukocyte scan also were > those of MRI (50 and 58%, respectively).

CONCLUSIONS

Leukocyte scanning is superior to MRI in detecting clinically unsuspected osteomyelitis in diabetic foot ulcers.
Chronic Sulfonylurea Therapy Augments Basal and Meal-Stimulated Insulin Secretion While Attenuating Insulin Responses to Sulfonylurea Per Se
Authors: McIntyre H David , Ma Alan , Bird Dominique M , Patterson Carol A , Cameron Donald P
Published: March 2007

OBJECTIVE

To examine changes in glycemia and insulin secretion in response to SU per se and in response to a standard diet plus OD or TD SU therapy during chronic GP and GB therapy.

RESEARCH DESIGN AND METHODS

Randomized (between agents and in order of dosing regimens), prospective, open, crossover study among 14 NIDDM patients to compare glucose, insulin, and C-peptide responses to a standard diet and to 10 mg of oral GP or GB taken without food 1) after 2 wk without therapy, 2) after 4 wk of either GP (n = 7) or GB (n = 7) treatment OD, and 3) after 4 wk of TD therapy with the same agent. Each patient received the same drug for maintenance therapy and for assessment of the response to the drug alone.

RESULTS

We observed a comparable reduction in overall glycemia with both agents, with more marked postprandial effects for GP. Similar glucose, insulin, and C-peptide profiles for both agents during OD and TD therapy. Augmented insulin secretion in response to meals contrasting with reduced insulinotropic effects of the drugs per se with chronic therapy.

CONCLUSIONS

Therapeutic equivalence of OD and TD dosing with GP and GB during chronic therapy. In view of the improved insulin secretion in response to nutrient stimuli, the attenuation of responses to SU per se during chronic therapy does not imply impairment of β-cell secretory capacity or represent a therapeutic disadvantage.
Impact of NIDDM on Mortality and Causes of Death in Pima Indians
Authors: Sievers Maurice L , Nelson Robert G , Knowler William C , Bennett Peter H
Published: March 2007

OBJECTIVE

To compare overall and cause-specific death rates for diabetic and nondiabetic Pima Indians.

RESEARCH DESIGN AND METHODS

This community-based study determined overall and cause-specific death rates in persons with and without NIDDM in the Pima population. Underlying causes of death for the 10-yr period from 1975 to 1984 were derived from review of death certificates and medical records. Diabetes diagnoses were based on an ongoing diabetes study initiated by the National Institutes of Health in 1965.

RESULTS

Of the 512 deaths, 241 were in Pima Indians with NIDDM; 203 (84%) of the deaths in diabetic subjects were attributed to natural causes (46 diabetic nephropathy, 35 IHD, 29 infections, 20 malignant neoplasms, 20 alcoholic liver disease, 18 stroke, 35 other causes). For natural causes, the overall age-sex-adjusted death rate in diabetic subjects was 1.7 times (95% CI 1.4–2.2) that in nondiabetic subjects. Longer duration of diabetes was significantly related to mortality, an association that was stronger in women than in men. Rates of death from diabetic nephropathy, IHD, and infections (but not stroke) were each significantly related to longer diabetes duration. Together, diabetic nephropathy and IHD accounted for 90% of the excess death rate among diabetic, compared with nondiabetic, Pimas.

CONCLUSIONS

In Pima Indians, NIDDM has a significant adverse effect on death rates that is directly related to diabetes duration, especially for deaths from diabetic nephropathy, IHD, or infections. Among the Pima, diabetic nephropathy is the leading cause of death, and IHD ranks second—a variation from other populations (in which IHD ranks first), probably partly attributable to a much younger age of onset of diabetes among the Pima than in the U.S. white population.
Renal Hemodynamics and Albumin Excretion Rate in Patients With Diabetes Secondary to Acquired Pancreatic Disease
Authors: Tiengo Antonio , Briani Giustina , Scaldaferri Ennio , Riva Fausto , Jori Elisabetta , Sgnaolin Elena , Fenato Rita , D'Ambrosio Michele , Fioretto Paola , Nosadini Romano , Crepaldi Gaetano , Trevisan Roberto
Published: March 2007

OBJECTIVE

To assess kidney function and AER in patients with PD.

RESEARCH DESIGN AND METHODS

Thirty-three patients with PD (age 52 ± 7 yr, duration of disease 11 ± 6 yr, BMI 24 ± 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection.

RESULTS

GFR and RPF were, respectively, 113 ± 35 and 441 ± 145 ml · min−1 · 1.73 m2 in patients with PD and 123 ± 30 and 549 ± 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 ± 0.05 vs. 0.22 ± 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml · min−1 · 1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 μg/min (range 1–186) in patients with PD and 11.2 (1–198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 μg/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER.

CONCLUSIONS

We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.
Diabetic Retinopathy in Oklahoma Indians With NIDDM: Incidence and risk factors
Authors: Lee Elisa T , Lee Vivian S , Kingsley Ronald M , Lu Min , Russell Dana , Asal Nabih R , Wilkinson C P , Bradford Reagan H
Published: March 2007

OBJECTIVE

To determine the incidence rates and risk factors for development of diabetic retinopathy in Oklahoma Indians.

RESEARCH DESIGN AND METHODS

Cohort follow-up study with baseline examination between 1972 and 1980 and follow-up examination between 1987 and 1991. Mean ± SD follow-up time was 12.8 ± 1.7 yr. Eleven Indian Health Service facilities (clinics and hospitals) in Oklahoma participated in the study. Study participants were a quasirandom sample of 1012 American Indians (379 men, 633 women) in Oklahoma with NIDDM, 927 of whom received a detailed eye examination at baseline. The mean age of participants was 52 yr with a duration of diabetes of 6.9 yr at baseline. The average quantum of Indian blood was 92% (77% full blood). At follow-up, 515 (55.6%) were alive, 408 (44.0%) were deceased, and 4 (0.4%) could not be traced. Of the living participants, 380 (73.8%) underwent an ophthalmoscopic examination.

RESULTS

The incidence of retinopathy among the participants who were free of disease at baseline and who survived the follow-up interval was 72.3%. By multivariate analysis, significant independent predictors of retinopathy recorded at baseline were FPG level, therapeutic regimen, systolic blood pressure, and duration of diabetes. FPG levels ≥ 11.1 mM (200 mg/dl) increased the risk of retinopathy 1.7 times that for levels < 7.8 mM (140 mg/dl). Insulin use was associated with a 20% greater incidence. Hypertension was a particularly significant risk factor for those with lower FPG levels.

CONCLUSIONS

Given that NIDDM is reaching epidemic proportions in Oklahoma Indians and that most may be afflicted with retinopathy, frequent ophthalmological examinations are clearly indicated for this high-risk population. The role of intervention, namely glycemic and hypertensive control, deserves further study.
Recent Developments in Metabolism That Impinge on Research into the Nature and Treatment of Diabetes Mellitus
Authors: Newsholme Eric A
Published: March 2007

It has been established that adenosine, its agonists, or antagonists can cause dramatic changes in insulin sensitivity in isolated soleus muscle and, moreover, can modify changes in sensitivity caused by pathophysiological conditions. Addition of adenosine deaminase to the incubation medium, which is known to lower the concentration of adenosine, increases the sensitivity of glycolysis to insulin. Addition of an adenosine-receptor agonist decreases sensitivity by about 10-fold, whereas addition of an adenosine-receptor antagonist increases sensitivity by about 10-fold. The latter totally removes the resistance of glucose utilization to insulin in the isolated soleus muscle obtained from either the genetically obese rat or from the rat fed a high sucrose diet. These findings strongly support the view that changes in insulin sensitivity in muscle can be brought about either by acute changes in the local concentration of adenosine or in the affinity or number of receptors for adenosine in muscle. However, in many of the conditions investigated, in which insulin sensitivity in muscle is changed, there was no correlation between the change in the adenosine content of the muscle and altered insulin sensitivity.

It has also been shown that prostaglandin E1 can increase dramatically the sensitivity of glycolysis to insulin and that this is a specific effect of prostaglandins of the E series. It is not produced by prostacyclins, thromboxanes, or leukotrienes. It is unclear if there is a relationship between the effects of adenosine and prostaglandins.

Chronic elevation of catecholamines may increase the sensitivity of glucose utilization to insulin and also increase the rate of thermogenesis by substrate cycling. Thus, resistance to catecholamines in muscle could result in both insulin resistance and impaired thermogenesis. Recent work has emphasized the important role of glutamine in the immune system, yet little or no work has been done on glutamine metabolism in diabetes mellitus.
Fuel and Fluid Homeostasis During Long-Term Exercise in Healthy Subjects and Type I Diabetic Patients
Authors: Koivisto Veikko A , Sane Timo , Fyhrquist Frej , Pelkonen Risto
Published: March 2007

OBJECTIVE

This study was designed to examine metabolic and hormonal effects of long-term exercise in healthy subjects and insulin-dependent (type I) diabetic patients.

RESEARCH DESIGN AND METHODS

Two studies were performed. First, 16 healthy males (32 ± 3 yr) were studied during a semitriathlon competition (2 km swimming, 90 km biking, and 21 km running). Second, 9 type I diabetic males (41 ± 2 yr) and 17 healthy matched control subjects were studied during a 75 km cross-country skiing race. Blood samples were taken before and immediately after exercise, and also during the ski race.

RESULTS

During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell. Apart from a fall in magnesium, serum electrolyte concentrations remained unchanged. Before long-term skiing, patients reduced their insulin dose by 30–40%. They were hyperglycemic during the initial part of the race, but near normoglycemic thereafter. There were large interindividual variations in the increments of counterregulatory hormones, whereas serum testosterone and luteinizing hormone fell quite uniformly. Plasma renin activity and aldosterone concentrations rose similarly in diabetic and healthy subjects, whereas the rise in antidiuretic hormone was slightly greater in diabetic patients. During the initial part of the race, serum atrial natriuretic peptide fell in both groups.

CONCLUSIONS

Severalfold increments in hormone concentrations contribute to the maintenance of fuel and fluid homeostasis during long-term exercise. With an appropriate adjustment of insulin dose and diet, also type I diabetic patients can participate in competitive long-term exercise.
Effect of Diabetes on Glucoregulation: From glucose transporters to glucose metabolism in vivo
Authors: Klip Amira , Marette André , Dimitrakoudis Dimitrios , Ramlal Toolsie , Giacca Adria , Shi Zhi Q , Vranic Mladen
Published: March 2007

Peripheral resistance to insulin is a prominent feature of both insulin-dependent and non-insulin-dependent diabetes. Skeletal muscle is the primary site responsible for decreased insulin-induced glucose utilization in diabetic subjects. Glucose transport is the rate-limiting step for glucose utilization in muscle, and that cellular process is defective in human and animal diabetes. The transport of glucose across the muscle cell plasma membrane is mediated by glucose transporter proteins, and two isoforms (GLUT1 and GLUT4) are expressed in muscle. Insulin acutely increases glucose transport in muscle by selectively stimulating the recruitment of the GLUT4 transporter (but not GLUT1) from an intracellular pool to the plasma membrane. In skeletal muscles of streptozocin-induced diabetic rats, there is a decreased GLUT4 protein content in intracellular and plasma membranes. In these rats, insulin induced the mobilization of GLUT4 from the internal pool, but the incorporation of the transporter protein into the plasma membrane is diminished. Conversely, the content of the GLUT1 transporter increases in the plasma membrane of these diabetic rats. Normalization of glycemia with phlorizin fully restores the amount of GLUT1 and GLUT4 proteins to normal levels in the plasma membrane without altering insulin levels. This suggests that glycemia regulates the number of glucose transporters at the cell surface, GLUT1 varying directly and GLUT4 inversely, to glycemia. The regulatory role of glycemia also can be seen in diabetic dogs in vivo, where correction of hyperglycemia with phlorizin restores, at least in part, the defective metabolic clearance rate of glucose seen in these animals. In addition to acutely stimulating glucose transport in muscle, insulin controls exercise- and possibly stress-mediated glucose uptake in vivo, by preventing hyperglycemia and by restraining the effects of catecholamines on lipolysis and/or muscle glycogenolysis. Finally, we postulated a neural pathway that requires the permissive effect of insulin to increase glucose uptake by the muscle. Thus, insulin, glucose, and neural pathways regulate muscle glucose utilization in vivo and are, therefore, important determinants of glucoregulation in diabetes.
Diabetes, Exercise, and Atherosclerosis
Authors: Ruderman Neil B , Schneider Stephen H
Published: March 2007

Regular exercise may diminish the risk for atherosclerotic vascular disease in patients with non-insulin-dependent (type II) diabetes and in the general population. The basis for this effect of exercise may be its ability to diminish or prevent hyperinsulinemia, insulin resistance, and/or increases in intra-abdominal adipose mass. These abnormalities are associated with premature atherosclerotic vascular disease, essential hypertension, type II diabetes, and certain dyslipoproteinemias, and most likely precede them. They also have been implicated in the pathogenesis of these disorders. We propose that the high prevalence of hyperinsulinemia and insulin resistance in individuals leading a western life-style accounts for the reported benefit of physical activity in preventing coronary heart disease in the general population. We also propose that exercise (and diet) are most likely to be effective when initiated in young individuals, before the onset of irreversible vascular alterations, and when life-style changes may be more acceptable. Early identification of such individuals may be possible on the basis of family history, the presence of components of the hyperinsulinemia-insulin resistance syndrome, and/or central obesity. One such group that may already have been identified is women with gestational diabetes.
Prevention of Early-Morning Hyperglycemia in IDDM Patients With Long-Acting Zinc Insulin
Authors: Parillo Mario , Mura Antonio , Iovine Ciro , Rivellese Angela A , Lavicoli Mario , Riccardi Gabriele
Published: March 2007

Objective

— To evaluate whether an insulin regimen with a long-acting zinc insulin (Ultratard HM) could help control fasting hyperglycemia in insulin-dependent diabetes mellitus (IDDM) patients.

Research Design And Methods

— A randomized sequential crossover trial with 6-wk treatment periods was used. Ten IDDM patients from the diabetes clinic at the Medical School who had persistent fasting hyperglycemia (> 10 mmol/L) were studied. Patients with nocturnal hypoglycemia were excluded. All patients completed the study. Insulin regimens consisted of three daily injections of a short-acting insulin (Actrapid HM) before meals and either a long-acting zinc insulin (Ultratard HM) or an intermediate isophane insulin (Protaphane HM) before the evening meal. Each regimen was followed for 6 wk.

Results

— Fasting blood glucose levels (at 06:00 and 08:00) were significantly lower after the long-acting insulin regimen (6.26 ± 0.88 vs. 10.82 ± 4.27 mM, P < 0.05 and 9.26 ± 1.02 vs. 14.03 ± 1.08 mM, < 0.05, respectively). Plasma-free insulin levels mirrored blood glucose concentrations because they were significantly higher at 06:00 and 08:00 after the long-acting insulin regimen (49.5 ± 10.1 vs. 20.1 ± 4.3 pM, P < 0.05 and 31.6 ± 5.0 vs. 16.5 ± 3.4 pM, P < 0.05, respectively). At any other time of the day, blood glucose and plasma insulin levels were not significantly different with either one of the two insulin regimens.

Conclusions

— A long-acting zinc human insulin injected before the evening meal can help to control persistent fasting hyperglycemia in IDDM patients.
Cardiorespiratory Fitness, Glycemic Status, and Mortality Risk in Men
Authors: Kohl Harold W , Gordon Neil F , Villegas Jesús A , Blair Steven N
Published: March 2007

Objective

— To determine the association of baseline cardiorespiratory fitness to all-cause mortality across the range of blood glucose levels.

Research Design And Methods

— Data from a prospective study of 8715 men (average age 42 yr), followed for an average of 8.2 yr (range 1-15 yr), were analyzed. Cardiorespiratory fitness was assessed by maximal-exercise treadmill testing. Men with evidence of clinical vascular disease or who did not achieve 85% of their age-predicted maximum heart rate during exercise testing were excluded from analyses.

Results

— Age-adjusted death rates increased with higher levels, of fasting blood glucose. Regardless of glycemic status, fit men had lower age-adjusted all-cause death rates than their less fit counterparts. For men with fasting blood glucose ≥ 7.8 mM or physician-diagnosed non-insulin-dependent diabetes mellitus (NIDDM), the age-adjusted death rates per 10,000 person-yr of follow-up in unfit and fit subjects were 82.5 and 45.9, respectively. The age-adjusted relative risk of death due to all causes was significantly elevated in the lower-fitness group within each of three glycemic status levels: fasting blood glucose <6.4 mM; relative risk (RR) = 1.93 (95% confidence interval [95% CI] 1.15-3.26); fasting blood glucose 6.4-7.8 mM; RR = 3.42 (95% CI 2.27-5.15); and fasting blood glucose ≥ 7.8 mM or with NIDDM, RR = 1.80 (95% CI = 1.25-2.58). Multivariate analyses, controlling for risk factors of mortality (age, resting systolic blood pressure, serum cholesterol, body mass index, family history of heart disease, follow-up interval, and smoking habit) showed a higher risk of death due to all causes for unfit compared with fit men. Multivariate risks of death associated with low fitness, compared with higher fitness (RR), in the three glycemic status groups were: fasting blood glucose <6.4 mM, RR = 1.38 (95% CI 1.09-1.74); fasting blood glucose 6.4-7.8 mM, RR = 1.61 (95% CI 0.91-2.86); and fasting blood glucose ≥7.8 mM or with NIDDM, RR = 1.92 (95% CI 0.75-4.90).

Conclusions

— These data suggest that risk of death increases with lessfavorable glycemic status, and that cardiorespiratory fitness may attenuate the forces of impaired carbohydrate metabolism on mortality from any cause.
Serum Cholesterol in Wisconsin Epidemiologic Study of Diabetic Retinopathy
Authors: Klein Barbara E K , Moss Scot E , Klein Ronald , Surawicz Tanya S
Published: March 2007

Objective

To describe serum total and high-density lipoprotein (HDL) cholesterol in a sample of people with diabetes.

Research Design and Methods

Subjects were those who participated in the 1984-1986 Wisconsin Epidemiologic Study of Diabetic Retinopathy. Data were from three groups of subjects: 304 younger-onset and 185 older-onset people taking insulin and 162 older-onset individuals not taking insulin. Serum lipids, duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, sex, age, serum creatinine, units of insulin per kiliogram per day, smoking status, serum C-peptide level, and alcohol use were analyzed statistically.

Results

In subjects taking insulin, glycosylated hemoglobin was correlated most strongly with total cholesterol. In those not taking insulin, C-peptide was correlated most strongly. In subjects taking insulin, the units used per day (fewer)and sex (female) were significantly associated with higher HDL cholesterol, and in both older-onset groups, serum C-peptide was significantly associated with lower HDL cholesterol. Mean total cholesterol levels were generally higher and mean HDL cholesterol levels were generally lower than those found in a nondiabetic comparison group.

Conclusions

By the National Cholesterol Education Program guidelines, 17% of younger-onset and 30% of older-onset insulin users and 32% of olderonset subjects not taking insulin were in the high-risk range for total cholesterol. Lower levels of glycosylated hemoglobin might result in lower cholesterol levels.
Insulin Resistance in Skeletal Muscles in Patients With NIDDM
Authors: Beck-Nielsen Henning , Vaag Allan , Damsbo Peter , Handberg Aase , Nielsen Ole Hother , Henriksen Jan Erik , Thye-Rønn Peter
Published: March 2007

Skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin; i.e., the effect of insulin on glucose disposal is reduced compared with the effect in control subjects. This defect has been found to be localized to the nonoxidative pathway of glucose disposal; hence, the deposition of glucose, as glycogen, is abnormally low. This defect may be inherited, because it is present in first-degree relatives to NIDDM patients two to three decades before they develop frank diabetes mellitus. The cellular defects responsible for the abnormal insulin action in NIDDM patients is reviewed in this article. The paper focuses mainly on convalent insulin signaling. Insulin is postulated to stimulate glucose storage by initiating a cascade of phosphorylation and dephosphorylation events, which results in dephosphorylation and hence activation of the enzyme glycogen synthase. Glycogen synthase is the key enzyme in regulation of glycogen synthesis in the skeletal muscles of humans. This enzyme is sensitive to insulin, but in NIDDM patients it has been shown to be completely resistant to insulin stimulation when measured at euglycemia. The enzyme seems to be locked in the glucose-6-phosphate (G-6-P)-dependent inactive D-form. This hypothesis is favored by the finding of reduced activity of the glycogen synthase phosphatase and increased activity of the respective kinase CAMP-dependent protein kinase. A reduced glycogen synthase activity has also been found in normoglycemic first-degree relatives of NIDDM patients, indicating that this abnormality precedes development of hyperglycemia in subjects prone to develop NIDDM. Therefore, this defect may be of primary genetic origin. However, it does not appear to be a defect in the enzyme itself, but rather a defect in the covalent activation of the enzyme system. Glycogen synthase is resistant to insulin but may be activated allosterically by G-6-P. This means that the defect in insulin activation can be compensated for by increased intracellular concentrations of G-6-P. In fact, we found that both hyperinsulinemia and hyperglycemia are able to increase the G-6-P level in skeletal muscles. Thus, insulin resistance in the nonoxidative pathway of glucose processing can be overcomed (compensated) by hyperinsulinemia and hyperglycemia. In conclusion, we hypothesize that insulin resistance in skeletal muscles may be a primary genetic defect preceding the diabetic state. The cellular abnormality responsible for that may be a reduced covalent insulin activation of the enzyme glycogen synthase. The compensation results in nearnormalization of glycogen synthesis, but the price diabetic subjects must pay to obtain this is hyperglycemia.
α-Glucosidase Inhibition by Miglitol in NIDDM Patients
Authors: Kingma Paulus J , Menheere Paulus PCA , Sels Jean P , Kruseman Arie C Nieuwenhuijzen
Published: March 2007

Objective

To determine the efficacy of the α-glucosidase inhibitor miglitol (BAYm 1099) regarding the starch content of food.

Research Design and Methods

Thirty-six non-insulin-dependent diabetes mellitus (NIDDM) subjects were studied in a double-blind randomized study comparing treatment with a single dosage of 100 mg miglitol or placebo and a single-blind crossover comparison of three test meals in which the carbohydrate contained either 30, 50, or 70% starch, and quantities of fat and protein were kept constant.

Results

Postprandial blood glucose excursions were reduced by ∼ 50% with miglitol after all test meals. In contrast, after miglitol treatment, maximum postprandial serum C-peptide and insulin values reached the same levels as after placebo treatment, although the time to reach these maximum levels was delayed. Free fatty acid values decreased after both miglitol and placebo similarly. Twenty-eight untoward events in 15 patients were reported in the miglitol treatment group and 11 events in 7 patients in the placebo treatment group.

Conclusions

Miglitol reduces postprandial blood glucose excursions independent of the starch content of the meal. Because no effects were found on incremental postprandial maximal levels of serum insulin and C-peptide, it may be that miglitol exerts, in addition to a delay of intestinal carbohydrate absorption, extraintestinal effects as well, particularly effects on disposition of glucose or anti-insulin counterregulatory factors.