bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Dyslipidemia in IPPM Patients
Authors: Garg Abhimanyu
Published: March 2007

Patients with insulin-dependent diabetes mellitus (IDDM) are at an increased risk for coronary heart disease. Factors that may enhance the risk include dyslipidemia, hypertension, and hyperglycemia. Until recently, the importance of dyslipidemia in IDDM was ignored because the prevalence of high cholesterol levels was similar to that in the nondiabetic population. However, unique abnormalities in the composition and metabolism of lipoproteins may occur in IDDM patients. Management of IDDM patients, therefore, should include control of dyslipidemia as well as control of hyperglycemia and hypertension. The therapeutic goals for serum cholesterol reduction in IDDM patients should be lower than that for nondiabetic patients, and the goals for children should be even lower than those for adults. Both very-low-density lipoprotein and low-density lipoprotein (LDL) levels should be the targets for therapeutic interventions and not just the LDL alone. Because of the unique features of dyslipidemia in IDDM patients, the therapeutic options may not be the same as that for nondiabetic patients. Hyperglycemia should be controlled by matching daily be low in saturated fats and cholesterol. If dyslipidemia persists despite diet and hyperglycemia management, drug therapy may be initiated. For IDDM children ≥ 10 years of age with elevated LDL-cholesterol levels, the first-line therapy should be bile acid sequestrants. For adults with IDDM, bile acid sequestrants also may be the drugs of choice, particularly for normotriglyceridemic patients. Nicotinic acid therapy should be avoided. Among other drugs, hydroxymethyl-glutaryl coenzyme A reductase inhibitors may be preferable for patients with elevated LDL cholesterol and borderline hypertriglyceridemia. Fibric acid derivatives should be used for markedly hypertriglyceridemic patients. The role of probucol for dyslipidemia in IDDM patients is not clear.
Comparative Pharmacokinetics and Glucodynamics of Two Human Insulin Mixtures 70/30 and 50/50 insulin mixtures
Authors: Woodworth James R , Howey Daniel C , Bowsher Ronald R , Brunelle Rocco L , Rowe Howard M , Compton Joyce , Cerimele Benito
Published: March 2007

OBJECTIVE

To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg.

RESEARCH DESIGN AND METHODS

We administered single doses of 50/50 and 70/30 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by at least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and Cpeptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (Cmax), time to maximum insulin concentration (tmax), terminal rate constant (β), area under the curve from 0 to ∞, (AUC x0), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [Cmin], time to minimum C-peptide concentration [tmin], area between the C-peptide baseline and the C-peptide suppression curve [AOCc], absolute maximal difference from baseline [Sdiff] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (Rmax) and time to Rmax (TRmax) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h (40Gtot) and total glucose infused (Gtot) during the study.

RESULTS

For the pharmacokinetic assessment, statistically greater values of insulin Cmax and β were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of Rmax and (40Gtot) found with the 50/50 mixture. Notably, differences were not detected for insulin AUCx0 and Gtot values.

CONCLUSIONS

Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.
The Role of Growth Hormone in the Development of Diabetic Retinopathy
Authors: Alzaid Aus A , Dinneen Sean F , Joseph Melton L , Rizza Robert A
Published: March 2007

OBJECTIVE

To determine the role of growth hormone (GH) in the development of diabetic retinopathy.

RESEARCH DESIGN AND METHODS

Medical records of 1,423 patients who had undergone insulin tolerance tests (1976–1991) at the Mayo Clinic were examined, and diabetic subjects were identified as either GH-deficient (GH increment after hypoglycemia <5 μg/L and peak <10 μg/L) or GH-suificient. Prevalence of retinopathy was determined in these cases and in a cohort group of diabetic subjects selected to match the GH-deficient cases. These control patients (32 cases) were selected from medical records of individuals who had received medical care at Mayo during the same interval but who had not undergone insulin tolerance testing.

RESULTS

Twenty-four patients with diabetes were identified, of whom 16 were GH-deficient and 8 GH-sufficient. Despite comparable age, duration of diabetes, and metabolic control, the prevalence of diabetic retinopathy in the GH-deficient group (2 of 16; 12.5%) was less (P < 0.05) than that observed in the GH-sufficient group (5 of 8; 62.5%). Prevalence in the GH-deficient group also was lower than that observed in the cohort control group (15 of 32, 47%).

CONCLUSIONS

These data strongly suggest that GH contributes to the development of diabetic retinopathy in humans.
Hypoqlycemia Increases Muscle Sympathetic Nerve Activity in IDDM and Control Subjects
Authors: Hoffman Robert P , Sinkey Christine A , Anderson Erling A
Published: March 2007

OBJECTIVE

The relationship between the increase in adrenomedullary catecholamine secretion and the sympathetic response to hypoglycemia is not well understood in humans. To explore this relationship more closely, we directly recorded muscle sympathetic nerve activity (MSNA) in control subjects and in insulin-dependent diabetes mellitus (IDDM) subjects without clinically evident diabetic complications.

RESEARCH DESIGN AND METHODS

Twelve IDDM subjects (22.5 ± 3.9 years of age, diabetes duration of 9.8 ± 8.3 years) and 12 age-matched control subjects were studied. MSNA was measured during insulin infusion (720 pM·m–2 ·min–1) with 30-min periods of 1) euglycemia, 2) hypoglycemia (target plasma glucose, 2.8 mM), and 3) recovery. The effect of increased insulin dose (1,440 pM· m–2 · min–1) was studied in six subjects in each group, and the effect of prolonged hypoglycemia (1 h) was studied in five IDDM subjects and four control subjects.

RESULTS

MSNA levels increased in IDDM and control subjects, 31 ± 8 and 29 ± 6%, respectively, above euglycemia during hypoglycemia and returned to euglycemic levels during recovery. MSNA levels during hypoglycemia were lower in IDDM subjects than in control subjects (26 ± 3 vs. 35 ± 2 bursts/min, P < 0.01). Importantly, no relationships were found between the MSNA and epinephrine responses to hypoglycemia in either group. Increasing the insulin infusion rate did not alter the MSNA response to hypoglycemia. During prolonged hypoglycemia, MSNA remained elevated above euglycemic levels throughout hypoglycemia.

CONCLUSIONS

These results demonstrate that insulin-induced hypoglycemia increases muscle sympathetic neural outflow in IDDM and control subjects. The lack of correlation between the MSNA and epinephrine responses to hypoglycemia indicates that the adrenomedullary and peripheral sympathetic responses to hypoglycemia are independently mediated.
Frequency of Severe Hypoglycemia in Patients With Type I Diabetes With Impaired Awareness of Hypoglycemia
Authors: Gold Ann E , Macleod Kenneth M , Frier Brian M
Published: March 2007

OBJECTIVE

To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospective assessment.

RESEARCH DESIGN AND METHODS

A prospective study was undertaken for 12 months in 60 patients with type I diabetes: 29 had impaired awareness of hypoglycemia and 31 retained normal awareness of hypoglycemia. The two groups of patients were matched for age, age at onset of diabetes, duration of diabetes, and glycemic control. Episodes of severe hypoglycemia were recorded within 24 h of the event and verified where possible by witnesses.

RESULTS

During the 12 months, 19 (66%) of the patients with impaired awareness had one or more episodes of severe hypoglycemia with an overall incidence of 2.8 episodes · patient–1 ·year–1. By comparison, 8 (26%) of the patients with normal awareness experienced severe hypoglycemia (P < 0.01) with an annual incidence of 0.5 episode · patient–1 · year–1 (P < 0.001). Severe hypoglycemia occurred at different times of the day in the two groups: patients with impaired awareness experienced a greater proportion of episodes during the evening (P = 0.03), and patients with normal awareness experienced a greater proportion in the early morning (P = 0.05). An assessment of fear of hypoglycemia revealed that patients with impaired awareness of hypoglycemia worried more about hypoglycemia than did patients with normal awareness (P = 0.008), but did not modify their behavior accordingly.

CONCLUSIONS

This prospective evaluation demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hypoglycemia, much of which occurred at home during waking hours.
Day-Night Blood Pressure Variation in Normotensive, Normoalbuminuric Type I Diabetic Subjects: Dippers and non-dippers
Authors: Gilbert Richard , Phillips Paddy , Clarke Caroline , Jerums George
Published: March 2007

OBJECTIVE

To examine day-night blood pressure (BP) variation in normotensive, normoalbuminuric subjects with type I diabetes and to assess the prevalence of an impaired nocturnal BP fall.

RESEARCH DESIGN AND METHODS

Fourteen healthy volunteers and 13 normotensive, normoalbuminuric subjects with type I diabetes were studied with an ambulatory sphygmomanometric device for 24 h.

RESULTS

No significant difference was found between diabetic and control groups with regard to daytime systolic blood pressure (sBP) or diastolic blood pressure (dBP). However, the mean nighttime sBPs (P < 0.01) and dBPs (P = 0.01) were significantly higher in the diabetic group compared with the control group. Furthermore, the night/day ratio for both sBP (P < 0.01) and dBP (P < 0.01) was significantly higher in the diabetic group. Approximately half of the diabetic subjects studied were non-dippers when defined either by a nocturnal fall in sBP/dBP of < 10/5 mmHg (5/13 vs. 0/14, P < 0.05: diabetic group vs. control group) or a day to night fall in either sBP (7/13 vs. 2/14, P < 0.05) or dBP (6/13 vs. 0/14, P < 0.01) of <10%.

CONCLUSIONS

Ambulatory BP may reveal impaired nocturnal BP fall in normotensive, normoalbuminuric subjects with type I diabetes. These subjects may be at greater risk of certain complications as a consequence of an increased BP burden.
Altered Postprandial Insulin Requirement in IDDM Patients With Gastroparesis
Authors: Ishii Masataka , Nakamura Teruo , Kasai Fukio , Onuma Tomio , Baba Tsuneharu , Takebe Kazuo
Published: March 2007

OBJECTIVE

To evaluate the effect of gastric emptying on postprandial insulinrequirement in insulin-dependent diabetes mellitus (IDDM) patients with and without gastroparesis.

RESEARCH DESIGN AND METHODS

Postprandial insulin requirement and gastric emptying were simultaneously evaluated in five IDDM patients with gastroparesis and in six control IDDM patients without gastroparesis. Postprandial insulin requirement after test-meal intake was assessed by measuring the insulin infusion rate during a 4-h feedback control with an artificial endocrine pancreas device (Biostator, Life Science Instruments, Miles, Elkhart, IN). Gastric solid and liquid emptyings were evaluated during the Biostator study by measuring the disappearance rate of 99mTc in the stomach and in the time course of plasma acetaminophen concentration, respectively.

RESULTS

Total insulin requirement during the first 120 min after the test-meal intake was significantly lower in the gastroparetic patients than in the control patients. The gastroparetic patients showed no apparent postprandial peak for insulin infusion rate during the 4-h study, although the peak rate was observed within 120 min after the test-meal intake in the control patients. The disappearance of 99mTc in the stomach was significantly slower, and plasma acetaminophen concentrations were significantlylower in the gastroparetic patients compared with those in the control patients, respectively.

CONCLUSIONS

The results suggest that IDDM patients with gastroparesis, accompanied by impaired solid and liquid emptying, have an altered postprandial insulin requirement.
Membrane Fluidity, Membrane Lipid Pattern, and Cytosolic Ca2+ Content in Platelets from a Group of Type II Diabetic Patients with Macrovascular Complications
Authors: Caimi Gregorio , Presti Rosalia Lo , Montana Maria , Canino Baldassare , Ventimiglia Giuseppe , Romano Adele , Catania Anna , Sarno Antonio
Published: March 2007

OBJECTIVE

To evaluate platelet membrane fluidity and some platelet metabolic parameters in type II diabetic patients with macrovascular complications.

RESEARCH DESIGN AND METHODS

In a group of 21 type II diabetic patients with macrovascular complications, we evaluated platelet membrane fluidity [marking intact resting platelets with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH)], platelet membrane lipid pattern (cholesterol :phospholipid [C:PL] ratio and individual phospholipids), and platelet cytosolic Ca2+ content (marking intact resting platelets with the fluorescent probe Fura 2AM).

RESULTS

Platelet membrane fluidity is decreased in type II diabetic patients with macrovascular complications compared with normal subjects (P < 0.001). Platelet membrane C:PL ratio and cytosolic Ca2+ content do not discriminate normal subjects from diabetic patients, and for individual phospholipids, only phosphatidylethanol-amine is decreased in diabetic patients compared with control subjects (P = 0.051). In normal subjects, the polarization degree of TMA-DPH is related to phosphatidylserine (P < 0.05) and phosphatidylcholine (P < 0.05), and in diabetic patients the polarization degree of TMA-DPH is related to C:PL ratio (P < 0.05) and sphyngomyelin (P < 0.05).

CONCLUSIONS

In type II diabetic patients with macrovascular complications, we observed an abnormality of platelet membrane fluidity, which may contribute to platelet functional alteration present in this clinical condition.
Pregnancy Outcomes in Women Without Gestational Diabetes Mellitus Related to the Maternal Glucose Level: Is there a continuum of risk?
Authors: Moses Robert G , Calvert Dennis
Published: March 2007

OBJECTIVE

To examine selected pregnancy outcomes in women without gestational diabetes mellitus to see whether there was a continuum of risk related to the maternal glucose level.

RESEARCH DESIGN AND METHODS

Consecutive women attending two prenatal clinics and three obstetricians in private practice were tested for GDM at the beginning of the third trimester using a 75-g glucose load in the fasting state. The rate of induction, the number of assisted deliveries, the presence of pregnancy-induced hypertension, fetal birth weights, and morbidity were examined with respect to the maternal 2-h glucose level.

RESULTS

Data were available for 1,441 women with a 2-h glucose level < 8.0 mmol/l (144 mg/dl). For each 1.0 mmol/l (18 mg/dl) increase in the glucose level, the odds in favor of an assisted delivery increased by 15.2%, and the odds in favor of the baby being admitted to a special care nursery (SCN) increased by 22.6%. There was no significant association between maternal glucose levels and the probability of either pregnancy-induced hypertension or a large-for-gestational-age (LGA) baby after adjustment for other variables.

CONCLUSIONS

In normal women there is a continuum of risk related to the maternal glucose level 2 h after a glucose tolerance test for the probability of having an assisted delivery and the likelihood of the baby being admitted to an SCN. The chance of having pregnancy-induced hypertension or a LGA baby also increased as the maternal glucose level increased but could be largely explained by an increasing body mass index.
Long-Term Glycemic Control Relates to Mortality in Type II Diabetes
Authors: Andersson Dan K , Svärdsudd Kurt
Published: March 2007

OBJECTIVE

To study the influence of long-term glycemic control on mortality in a cohort of newly detected type II diabetic individuals.

RESEARCH DESIGN AND METHODS

A total of 411 newly detected type II diabetic individuals diagnosed between 1972 and 1987 were followed until 31 December 1989. Clinical data concerning fasting blood glucose (FBG) values, body mass index (BMI), type of treatment, and concomitant diseases were collected during 8 randomly selected years. Long-term glycemic control was measured as annual averages of FBG values during these years. Mortality data were obtained from official registers.

RESULTS

There were 161 diabetic subjects who died during a mean follow-up time of 7.4 years. In univariate analyses, higher age at diagnosis; higher baseline or average FBG; and the presence of heart disease, cerebrovascular disease, or kidney disease at the beginning or during the course of diabetes were related to higher mortality. Type of diabetes treatment or having a diagnosis of hypertension was not related to mortality. In multiple logistic regression analyses, age at diagnosis and average FBG were independently related to all-cause (P = 0.0002), cardiovascular (P = 0.0006), and ischemic heart disease mortality (P = 0.03). No correlations between glycemic control and noncardiovascular deaths were found. In a Cox's regression analysis, average FBG was significantly related to length of survival when age at diabetes diagnosis was taken into account (P < 0.05). Diabetic subjects with average FBG ≥ 7.8 mmol/l had 50% higher mortality compared with diabetic subjects with average FBG < 7.8 mmol/l.

CONCLUSIONS

Diabetic patients with good long-term glycemic control had a better survival rate than subjects with high average FBG values. The findings should be interpreted cautiously because possible confounding factors such as dyslipoproteinemia and smoking were not studied.
The Use of Areas Under Curves in Diabetes Research
Authors: Allison David B , Paultre Furcy , Maggio Carol , Mezzitis Nicholas , Pi-Sunyer F Xavier
Published: March 2007

Recently, several articles appearing in the diabetes literature have suggested that many investigators are unclear about a number of issues involving the use of areas under the curve (AUCs). This prompted us to reconsider issues in the calculation, use, meaning, and presentation of AUCs. We discuss five issues: 1) What is a curve and an area? 2) How should one graphically present a group's curve? 3) How should one calculate AUCs? 4) Should one subtract baseline values from outcome values before calculating AUCs? And 5) are AUCs the best way to combine multiple readings into a single index?
Incidence and Prevalence of Childhood Diabetes in Slovakia (1985–1992)
Authors: Michalková Dagmar M , Černay Jozef , Danková Anna , Rusnák Martin , Fandáková Katarína ,   Slovak Childhood Diabetes Epidemiology Study Group
Published: March 2007

OBJECTIVE

To provide reliable data on the incidence and prevalence of insulin–dependent diabetes mellitus (IDDM) in children in Slovakia.

RESEARCH DESIGN AND METHODS

A total of 754 Slovak children with IDDM, aged 0–14 years, were identified during an 8-year study period. There were 369 boys and 385 girls from an average population of 1,363,499 children. All patients were prospectively recorded. The primary ascertainment was based on notifications by physicians from outpatient departments. The second independent source of information was from all hospitals where the diabetic patients were hospitalized. The completeness of ascertainment was based on the capture-recapture procedure.

RESULTS

The completeness of the ascertainment was 95%. In 1992, the annual incidence rate of IDDM (per 100,000) in the 0- to 14-year-old age-group was 8.92 for both sexes (7.95 for boys and 9.93 for girls). In the youngest age-group, an increase in the incidence rates from 2.89 in 1985 to 6.54 in 1992 was observed. Seasonality, with a higher incidence in autumn and winter, was observed in children older than 4 years. The prevalence rates of IDDM (per 1,000) were 0.28–0.50% in the 8-year period.

CONCLUSIONS

The incidence of IDDM in Slovak children (0–14 years) is similar to what has been found in other Central European countries. In children younger than 4 years of age, in the last 2 years (1991 and 1992) more patients with diabetes were found than in any period during the preceding 6 years. The recent conspicuous increase in the incidence of IDDM among the younger children in Slovakia urges us to study its mechanisms, so far unknown, and to search for possible means of prevention.
Glucose, Insulin, and Glucagon Levels During Exercise in Pancreas Transplant Recipients
Authors: Redmon J Bruce , Kubo Spencer H , Robertson R Paul
Published: March 2007

OBJECTIVE

To determine whether pancreas transplant recipients maintain normal blood glucose levels during physical exercise.

RESEARCH DESIGN AND METHODS

We measured serum glucose, insulin, C-peptide, and plasma glucagon levels in six pancreas transplant recipients and six healthy control subjects matched for age, sex, body size, and level of conditioning during 1 h of bicycle exercise at a workload set to achieve 40% of each individual's previously determined peak oxygen consumption (VO2).

RESULTS

Serum glucose values were not different between control subjects and transplant recipients before the start of exercise (5.0 ± 0.1 and 4.9 ±0.1 mmol/l, respectively). Serum glucose levels fell slightly but significantly in both recipients and control subjects during exercise. There were no significant differences in glucose levels between the two groups at any time point during exercise, although mean nadir glucose during exercise was slightly lower in transplant recipients compared with control subjects (4.4 ± 0.1 vs. 4.8 ± 0.1 mmol/l, P = 0.04). In control subjects, insulin and C-peptide levels fell significantly within 15–30 min of exercise and glucagon levels rose significantly after 60 min of exercise. In transplant recipients, there was a trend for insulin and C-peptide levels to fall and glucagon levels to rise during exercise, although these changes were delayed and were not statistically significant.

CONCLUSIONS

No significant abnormalities in blood glucose were detected in pancreas transplant recipients during bicycle exercise at 40% of peak VO2 for 1 h. Compared with levels in control subjects, subtle alterations in insulin and glucagon levels may occur in transplant recipients during exercise. However, these alterations do not appear to result in either hyperglycemia or hypoglycemia during light exercise for up to 1 h.
Screening for Diabetes Mellitus in Adults: The utility of random capillary blood glucose measurements
Authors: Engelgau Michael M , Thompson Theodore J , Smith Philip J , Herman William H , Aubert Ronald E , Gunter Elaine W , Wetterhall Scott F , Sous Edward S , Ali Mohamed A
Published: March 2007

OBJECTIVE

Because half of the people with non-insulin-dependent diabetes mellitus (NIDDM) are undiagnosed and because near-normal glycemic control can prevent diabetic complications, we evaluated the use of field-based random capillary blood glucose measurement as a screening test for NIDDM.

RESEARCH DESIGN AND METHODS

A cross-sectional sample of 828 Egyptians ≥20 years of age underwent both a random capillary blood glucose measurement performed with a portable reflectance meter in the field and an oral glucose tolerance test in the laboratory. The sensitivity and specificity of random capillary blood glucose measurements in predicting the presence of NIDDM were evaluated.

RESULTS

Multivariate analyses showed that the screening test performed better when subjects had eaten shortly before the test (area under receiver operating characteristic curve, 0.87 for a 1-h postprandial period compared with 0.69 for an 8-h postprandial period) and that the optimal capillary blood glucose cutoff points to define a positive test increased with age. For a postprandial period of 1 h, cutoff points of 115 mg/dl for individuals 30 years of age and 140 mg/dl for those 75 years of age yielded similar performance characteristics (sensitivity 82% and specificity 78% for those 30 years old; sensitivity 81% and specificity 80% for those 75 years old).

CONCLUSIONS

Adjusting random capillary blood glucose measurements for the postprandial period and using age-specific cutoff point values can improve performance of the screening test.
Reduced Awareness of Hypoglycemia in Adults With IDDM: A prospective study of hypoglycemic frequency and associated symptoms
Authors: Clarke William L , Cox Daniel J , Gonder-Frederick Linda A , Julian Diana , Schlundt David , Polonsky William
Published: March 2007

OBJECTIVE

To prospectively evaluate the frequency and severity of hypoglycemic episodes in IDDM subjects who declare themselves to have reduced awareness of hypoglycemia, to validate their self-designations in their natural environment, and to determine objectively the presence or absence of autonomic and neuroglycopenic symptoms associated with their low blood glucose (BG) levels.

RESEARCH DESIGN AND METHODS

A total of 78 insulin-dependent diabetes mellitus (IDDM) subjects (mean age 38.3 ± 9.2 years; duration of diabetes 19.3 ± 10.4 years) completed two sets of assessments separated by 6 months. The assessments included reports of frequency and severity of low BG, symptoms associated with low BG, and a BG symptom/estimation trial using a hand-held computer (HHC). Diaries of hypoglycemic episodes were kept for the intervening 6 months. HbA1 levels were determined at each assessment.

RESULTS

Of the subjects, 39 declared themselves as having reduced awareness of hypoglycemia (reduced-awareness subjects). There were no differences between these reduced-awareness subjects and aware subjects with regard to age, sex, disease duration, insulin dose, or HbA1. During the HHC trials, reduced-awareness subjects were significantly less accurate in detecting BG < 3.9 mmol/l (33.2 ± 47 vs. 47.6 ± 50% detection, P = 0.001) and had significantly fewer autonomic (0.41 ± 0.82 vs. 1.08 ± 1.22, P = 0.006, reduced-awareness vs. aware) and neuroglycopenic (0.44 ± 0.85 vs. 1.18 ± 1.32, P = 0.004, reduced-awareness vs. aware) symptoms per subject. Prospective diary records revealed that reduced-awareness subjects experienced more moderate (351 vs. 238, P = 0.026) and severe (50 vs. 17, P = 0.0062) hypoglycemic events. The second assessment results were similar to the first and verified the reliability of the data.

CONCLUSIONS

IDDM subjects who believe they have reduced awareness of hypoglycemia are generally correct. They have a history of more moderate and severe hypoglycemia, are less accurate at detecting BG < 3.9 mmol/l, and prospectively experience more moderate and severe hypoglycemia than do aware subjects. Neither disease duration nor level of glucose control explains their reduced awareness of hypoglycemia. Reduced-awareness individuals may benefit from interventions designed to teach them to recognize all of their potential early warning symptoms.
Tolrestat in the Primary Prevention of Diabetic Neuropathy
Authors: Giugliano Dario , Acampora Rita , Marfella Raffaele , Maro Giosué Di , Rosa Nicoletta De , Misso Lucio , Ceriello Antonio , Quatraro Antonio , D'Onofrio Felice
Published: March 2007

OBJECTIVE

To compare the effects of tolrestat and placebo in patients with subclinical diabetic neuropathy.

RESEARCH DESIGN AND METHODS

Non-insulin-dependent diabetes mellitus (NIDDM) patients with early involvement of the autonomic nervous system were identified by only one pathological (outside the 99% confidence interval of the normal population) squatting test (vagal or sympathetic). Fifty-seven patients entered a randomized, placebo-controlled, double-blind, parallel 52-week study of tolrestat at a dose of 200 mg/day. Cardiovascular reflex tests (squatting vagal and sympathetic tests, pressure gain, deep breathing, lying-to-standing, Valsalva maneuver, and orthostatic hypertension), vibration thresholds, tendon reflexes, and muscle strength were assessed throughout the study.

RESULTS

At 12 months, nerve function significantly improved in patients receiving tolrestat and deteriorated in patients taking placebo. At baseline, the squatting vagal test was normal in 16 patients in the tolrestat group and in 15 patients in the placebo group. At 12 months, 25 patients taking tolrestat had a normalized squatting test, but only 6 patients taking placebo did (P = 0.02). Vibration perception threshold improved by a value of 6 ± 3 V in the tolrestat group (P < 0.001) and deteriorated by a value of 3 ± 1.8 V (P < 0.001) in the placebo group.

CONCLUSIONS

Tolrestat may be useful in the primary prevention of diabetic neuropathy.
Postural Stability in Diabetic Polyneuropathy
Authors: Boucher Pierre , Teasdale Normand , Courtemanche Richard , Bard Chantal , Fleury Michelle
Published: March 2007

OBJECTIVE

To examine whether sensory changes in lower limbs associated with diabetic sensory polyneuropathy compromise postural stability in different visual sensory conditions.

RESEARCH DESIGN AND METHODS

The presence and seventy of sensory neuropathy was evaluated with a clinical scale and measures of nerve conduction velocity in the lower limbs. Balance control was evaluated by testing subjects' postural stability (with a force platform) with vision, without vision, and during a recovery period after being without vision.

RESULTS

Neuropathic patients showed larger ranges of sway, a faster sway speed, and a greater dispersion of sway than control subjects in all conditions. They also exhibited similar or less stable postural performance with vision than that of control subjects without vision. There was a strong relationship between the severity of the neuropathy and the postural stability.

CONCLUSIONS

This experiment highlights that even with vision, the postural stability of neuropathic patients is impaired and may put them at higher risk of falling when performing more challenging daily tasks.
Clinical Management of the NIDDM Patient: Impact of the American Diabetes Association Practice Guidelines, 1985–1993
Authors: Stolar Mark W ,   Endocrine Fellows Foundation Study Group
Published: March 2007

OBJECTIVE

To assess the impact of the American Diabetes Association's (ADA's) standards of care for patients with non-insulin-dependent diabetes mellitus (NIDDM) on practice patterns among university-based endocrine physicians and fellows.

RESEARCH DESIGN AND METHODS

This study represents a retrospective chart-based review of 790 patients with NIDDM conducted by endocrine fellows in training at 42 academic institutions. By using an ADA guidelines-based questionnaire, patient management and adherence to the guidelines were assessed by reviewing charts dating ≥3 years before, the year of, and 3 years after the guidelines' publication. All calculations were performed using the McNemar test, and all P values are two-sided.

RESULTS

The ADA standards of care have not had the significant impact in the clinical training setting that was anticipated. Deficiencies were noted in all aspects of the diabetic patient encounter and did not improve significantly following publication of the guidelines, except in the areas of foot care, eye examination, and lipid screening. Major deficiencies exist in areas of quality assurance and chart documentation, and these did not improve over time.

CONCLUSIONS

New strategies must be devised to increase awareness and implementation of these guidelines, both to enhance patient care and to improve the training of future diabetes caregivers.
The Epidemiology of Diabetes and Pregnancy in the U.S., 1988
Authors: Engelgau Michael M , Herman William H , Smith Philip J , German Robert R , Aubert Ronald E
Published: March 2007

OBJECTIVE

To determine the prevalence of pregnancy complicated by diabetes in a representative sample of the U.S. population.

RESEARCH DESIGN AND METHODS

We analyzed data from a multistaged cross-sectional probability sample of live births recorded in the U.S. in 1988 for women 15–49 years of age. The main outcome measure was pregnancy complicated by diabetes.

RESULTS

Diabetes was present in congruent to 154,000 (4%) of all pregnancies in the U.S. Gestational diabetes mellitus (GDM) accounted for 135,000 of such pregnancies (88%), non-insulin-dependent diabetes mellitus (NIDDM) for 12,000 (8%), and insulin-dependent diabetes mellitus for 7,000 (4%). On average, the mothers with NIDDM (29.6 years) and GDM (29.3 years) were older than mothers whose pregnancies were not complicated by diabetes (26.2 years; P < 0.05). In multivariate analyses, the odds of having a pregnancy complicated by GDM increased significantly with maternal age and body mass index.

CONCLUSIONS

Pregnancy is complicated by diabetes more often than was previously believed. More frequent testing may further increase the apparent prevalence of GDM.
High Incidence of Childhood-Onset IDDM in Kuwait
Authors: Shaltout Azza A , Qabazard Mariam A , Abdella Nabila A , LaPorte Ronald E , Arouj Mounira Al , Nekhi Abdulla Ben , Moussa Mohamed A , Khawari Mona A Al ,   Kuwait Study Group of Diabetes in Childhood
Published: March 2007

OBJECTIVE

To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in children aged 0–14 years in Kuwait, as part of the World Health Organization Multinational Collaborative Study (DIAMOND), and to determine if the incidence rates have increased.

RESEARCH DESIGN AND METHODS

All cases of IDDM diagnosed before the child's 15th birthday between 1 January 1992 and 31 December 1993 were recorded. Prospective notification of all children with newly diagnosed diabetes who were admitted to hospitals and periodic review of hospital medical records provided the primary source; notification by physicians working in diabetic clinics, in which registry of all new cases is mandatory, provided the secondary source of ascertainment.

RESULTS

The degree of ascertainment was 92.2%. The annual incidence of IDDM for children aged 0–14 years over the 2-year period was 15.4/100,000 (95% confidence interval, 12.4–19), with a male:female ratio of 1.2:1. The age-specific annual incidence rates for the age-groups 0–4, 5–9, and 10–14 years were 12.8, 15.1, and 18.3/100,000, respectively, with a male:female ratio of 1.45:1 in the 0- to 4-year-old age-group and an equal sex ratio in the 5- to 9- and 10- to 14-year-old age-groups. No significant difference was detected between incidence rates of IDDM in boys and girls in the three age-groups. There was no significant linear trend toward an increase in IDDM incidence rates as age advanced. Compared with a previous study by Taha et al. (Taha T, Moussa M, Rashed A, Fenech F: Diabetes mellitus in Kuwait: incidence in the first 29 years of life. Diabetologia 25:306–308, 1983), there was a nearly fourfold increase of IDDM in the age-group 0–14 years, mainly in those children < 5 years old, suggesting a rapid increase in a short period of time.

CONCLUSIONS

Kuwait has the highest incidence of IDDM in children in the region, and an apparently increasing incidence has been demonstrated over the last decade.
The Influence of Pregnancy on IDDM Complications
Authors: Hemachandra Anusha , Ellis Demetrius , Lloyd Cathy E , Orchard Trevor J
Published: March 2007

OBJECTIVE

Although pregnancy has been associated with an increased progression of certain insulin-dependent diabetes mellitus (IDDM) complications, particularly retinopathy, both the short- and long-term relationships between pregnancy and both neuropathy and macrovascular disease are poorly documented. This study was conducted to comprehensively examine the influence of pregnancy on the development and progression of IDDM complications.

RESEARCH DESIGN AND METHODS

Using the Pittsburgh Epidemiology of Diabetes Complications Study population (childhood-onset IDDM), two nested, pair-matched case-control studies were conducted. Women who had completed at least one successful pregnancy (n = 80) were matched to women with no history of pregnancy by age, duration of IDDM, race, and marital history. The first nested study (study 1) compared the prevalences of five IDDM complications between case and control groups. The second nested study (study 2) compared the incidences of the same five complications over an approximate 2-year interval during which the case subjects (n = 30) completed a successful pregnancy.

RESULTS

There were no significant differences in the prevalence rates of coronary heart disease, neuropathy, proliferative retinopathy, lower extremity arterial disease, and overt nephropathy by case-control status, while parity did not predict any complication in multiple logistic analysis (study 1). In study 2, there were small but nonsignificant differences in incidence rates of overt nephropathy and lower extremity arterial disease between the groups, whereas case subjects had almost 3 times the incidence rate of proliferative retinopathy (P = 0.58) and 10 times the incidence rate of neuropathy (P < 0.001) as did other matched control subjects. In multivariate analysis, parity predicted neuropathy incidence but did not predict the incidence of any other complication, including proliferative retinopathy.

CONCLUSIONS

Women with IDDM who experience a pregnancy may not be at an increased risk of diabetes complications later in life. However, in the short term, pregnancy may accelerate the development of some complications, such as neuropathy.
Angiotensin I-Converting Enzyme Gene Polymorphism Is Associated With Myocardial Infarction, but Not With Retinopathy or Nephropathy, in NIDDM
Authors: Fujisawa Tomomi , Ikegami Hiroshi , Shen Gong-Qing , Yamato Eiji , Takekawa Kiyoshi , Nakagawa Yusuke , Hamada Yoichi , Ueda Hironori , Rakugi Hiromi , Higaki Jitsuo , Ohishi Mitsuru , Fujii Kenshi , Fukuda Masakatsu , Ogihara Toshio
Published: March 2007

OBJECTIVE

To clarify the relationship between the angiotensin I-converting enzyme (ACE) gene polymorphism and diabetic micro- and macroangiopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS

We examined 267 NIDDM patients with various stages of diabetic retinopathy, 61 patients with myocardial infarction (MI), and 136 patients without MI. An insertion/deletion polymorphism of the ACE gene was typed by polymerase chain reaction.

RESULTS

Although no association was found between ACE gene polymorphism and diabetic retinopathy or nephropathy, this polymorphism was associated with MI in the patients with NIDDM. Homozygotes for the deletion polymorphism (DD genotype) were found more frequently in diabetic patients with MI (31.1%) than in diabetic patients without ischemic heart disease (16.9%), with a relative risk of 2.22 (95% confidence interval 1.11–4.46, P = 0.024).

CONCLUSION

These data indicate that ACE gene polymorphism is associated with MI, but not with retinopathy or nephropathy, in patients with NIDDM and suggest that the ACE gene confers susceptibility to diabetic macroangiopathy but not to microangiopathy.
Exocrine Pancreatic and β-cell Function in Malnutrition-Related Diabetes Among North Indians
Authors: Bhatia Eesh , Baijal Sanjay S , Kumar K Ramesh , Choudhuri Gourdas
Published: March 2007

OBJECTIVE

To compare the pancreatic exocrine and β-cell function in the two variants of malnutrition-related diabetes mellitus (MRDM): fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD).

RESEARCH DESIGN AND METHODS

Fecal chymotrypsin (FCT) and fasting C-peptide levels were measured in 20 consecutive patients with FCPD and 19 with PDPD. FCPD was diagnosed by pancreatic calcification on ultrasonography, while the diagnosis of PDPD was made on the basis of low body mass index, severe diabetes requiring insulin therapy, and ketosis resistance on interruption of insulin. Twenty patients with type I diabetes and 32 healthy subjects served as control subjects.

RESULTS

Both FCPD and PDPD patients had diminished levels of FCT when compared with those of control subjects and patients with type I diabetes. However, FCT levels were significantly lower in subjects with FCPD (median 0.4 U/g, range 0–8.9 U/g), in comparison with those with PDPD (4.7 U/g, 0.6–40.5 U/g; P < 0.001). Of the FCPD patients, 13 of 20 (65%) had severe exocrine pancreatic deficiency (FCT < 1 U/g) vs. 3 of 19 (15.8%) PDPD subjects (P < 0.01). In comparison with control subjects, fasting serum C-peptide levels were significantly diminished in both MRDM groups. However, C-peptide levels in subjects with FCPD (mean ± SE, 0.22 ± 0.04 nmol/l) and PDPD (0.26 ± 0.04 nmol/l) were comparable.

CONCLUSIONS

Among the two variants of MRDM, subjects with FCPD have severe pancreatic exocrine deficiency in comparison with those with PDPD, even though their C-peptide levels are comparably diminished. This suggests that the pathogenesis of these two entities may differ or that the genetic and/or environmental factors leading to exocrine damage are different.
Nondiabetic Mexican-Americans Do Not Have Reduced Insulin Responses Relative to Nondiabetic Non-Hispanic Whites
Authors: Haffner Steven M , Miettinen Heikki , Stern Michael P
Published: March 2007

OBJECTIVE

To study why Mexican-Americans have a threefold increase in NIDDM relative to non-Hispanic whites. The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion proposed as precursors of NIDDM.

RESEARCH DESIGN AND METHODS

We examined possible ethnic differences in fasting insulin (as a marker of insulin resistance) and change in insulin-to-change in glucose ratio (ΔI30:ΔG30) during the first 30 min after oral glucose ingestion (as a marker of abnormal whites from the San AntonioHeart Study, a population-based study of diabetes and cardiovascular disease. Fasting insulin and ΔI30:ΔG30 were evaluated as continuous variables.

RESULTS

Mexican-Americans had increased insulin concentrations at fasting and 30, 60, and 120 min after an oral glucose load as well as an increased 0- to 30-min increment in insulin and ΔI30:ΔG30 relative to non-Hispanic whites. These results remained unchanged after adjustment for age, sex, obesity, body fat distribution, and glucose tolerance.

CONCLUSIONS

These results suggest that increased insulin resistance rather than decreased insulin secretion is characteristic of nondiabetic Mexican-Americans, a high-risk population for NIDDM.
Depression and Risk for Onset of Type II Diabetes: A prospective population-based study
Authors: Eaton William W , Armenian Haroutune , Gallo Joseph , Pratt Laurie , Ford Daniel E
Published: March 2007

OBJECTIVE

To determine whether depression is associated with an increased risk for onset of diabetes.

RESEARCH DESIGN AND METHODS

In 1981, a total of 3,481 household-residing adults participated in the Epidemiologic Catchment Area (ECA) Program survey at the East Baltimore site. A follow-up of that cohort after 13 years completed 1,897 interviews, amounting to >72% of survivors. In 1981, depression was assessed with the National Institutes of Mental Health (NIMH) Diagnostic Interview Schedule and diabetes, by self-report. This prospective analysis focused on subjects at risk for onset of diabetes by removing from the analysis individuals with diabetes in 1981.

RESULTS

There were 89 new cases of diabetes among 1,715 individuals at risk, yielding a 13-year cumulative incidence of diabetes of 5.2%. In logistic models, major depressive disorder, but not milder forms of depression or other forms of psychiatric disorder, predicted the onset of diabetes (estimated relative risk, 2.23; 95% CI 0.90–5.55). Controlling for age, race, sex, socioeconomic status, education, use of health services, other psychiatric disorders, and body weight did not weaken the relationship.

CONCLUSIONS

Major depressive disorder signals increased risk for onset of type II diabetes. Limitations of the findings arise from the difficulty in determining temporal order with two chronic conditions, even when the temporal order of measurement is clear. In addition, even though control variables were introduced for the use of health services, it is possible that the treatment for depression led to an earlier diagnosis of diabetes in this sample.
Fibrocalculous Pancreatic Diabetes: Long-term survival analysis
Authors: Mohan Viswanathan , Premalatha Gopal , Padma Audinarayanan , Chari Suresh T , Pitchumoni Capecomorin S
Published: March 2007

OBJECTIVE

To determine the long-term survival and causes of death in fibrocalculous pancreatic diabetes, a form of diabetes secondary to tropical chronic pancreatitis.

RESEARCH DESIGN AND METHODS

A cohort of 370 patients with fibrocalculous pancreatic diabetes were analyzed with respect to survival time from the date of occurrence of the first symptom of the disease as well as after the onset of diabetes. The cause of death was analyzed in the patients who died. Cumulative survival rates were calculated by the actuarial method, and life table graphs were plotted by mathematical calculations.

RESULTS

Long-term survival of patients with fibrocalculous pancreatic diabetes is much better today than that described 30 years ago. About 80% of patients were alive 35 years after the first episode of abdominal pain. The median survival time after the diagnosis of diabetes was 25 years. These figures, however, are still considerably lower than the life expectancy of the age- and sex-matched general population. Diabetic nephropathy was the main cause of death. Pancreatic cancer and other chronic pancreatitis-related causes as well as malnutrition and infections were also important contributors to mortality.

CONCLUSIONS

The overall prognosis for patients with fibrocalculous pancreatic diabetes appears to have improved possibly because of earlier diagnosis, better management of diabetes, and improved nutrition.
Insulin-Induced Lipoatrophy in Type I Diabetes: A possible tumor necrosis factor-α-mediated dedifferentiation of adipocytes
Authors: Atlan-Gepner Catherine , Bongrand Pierre , Farnarier Catherine , Xerri Luc , Choux Régine , Gauthier Jean-Francois , Brue Thierry , Vague Philippe , Grob Jean-Jacques , Vialettes Bernard
Published: March 2007

OBJECTIVE

To test the hypothesis that tumor necrosis factor (TNF)-α may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions.

RESEARCH DESIGN AND METHODS

An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-α and interleukin (IL)-6 production from PBMC in presence of insulin were studied.

RESULTS

The production of TNF-α and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone.

CONCLUSIONS

In our reported case, a local hyperproduction of TNF-α from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.