bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycemic Control in a Sample of Black and White Clinic Patients with NIDDM
Authors: Weatherspoon Lorraine J , Kumanyika Shiriki K , Ludlow Robert , Schatz Desmond
Published: March 2007

OBJECTIVE

To compare glycemic control of black and white patients under treatment for non-insulin-dependent diabetes mellitus (NIDDM).

RESEARCH DESIGN AND METHODS

Medical records of patients with NIDDM were reviewed at 19 of 24 clinics or health centers in a specified area of north central Florida. Data were abstracted from the charts of all non-Hispanic black (n = 248) or white (n = 280) patients who met preset eligibility criteria.

RESULTS

The mean ± SD age was 58 ± 14 years; the mean ± SD duration of diabetes was 9 ± 7.5 years. Of 528 patients, 220 were treated with oral hypoglycemic agents, 269 were treated with insulin, 28 were treated with diet alone, and 11 were treated with a combination of oral agents, diet, and insulin. Glycosylated hemoglobin was ≥8% for 47% of black women, 41% of black men, 38% of white men, and 29% of white women. The less favorable control status of the black women persisted within categories of age (40–59 years or ≥60 years), treatment (insulin or oral hypoglycemic agents), time since diagnosis (less than versus greater than or equal to the median of 7 years), and obesity (noted versus not noted in chart). In multiple logistic regression analyses controlling simultaneously for these variables, the odds (95% confidence interval [CI]), compared with white women, of having glycosylated hemoglobin ≥8% were 2.2 (1.4, 3.4) for black women and 1.5 (0.8, 2.9) and 1.4 (0.8, 2.5) for black and white men, respectively.

CONCLUSIONS

Black women were more likely than white women or men to have glycosylated hemoglobin ≥8%. This difference was not readily explained by age, type of treatment, time since diagnosis, or a notation of obesity in the medical record, although an effect of obesity cannot be excluded on this basis.
Greater Effect of Diabetes on LDL size in Women Than in Men
Authors: Haffner Steven M , Mykkänen Leena , Stern Michael P , Paidi Michael , Howard Barbara V
Published: March 2007

OBJECTIVE

Coronary heart disease (CHD) is increased two- to fourfold in subjects with NIDDM compared with normoglycemic subjects. This excess risk is only partially explained by conventional risk factors. We studied the effect of non-insulin-dependent diabetes mellitus (NIDDM) on the size of low-density lipoproteins (LDL).

RESEARCH DESIGN AND METHODS

We examined the effect of NIDDM on LDL size and subclass pattern B (LDL size < 253.5 Å) in 95 diabetic subjects and 371 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease.

RESULTS

LDL size (Å) was significantly lower in diabetic subjects (men: 252.2 ± 1.8; women: 254.7 ± 1.3) than in nondiabetic subjects (men: 256.1 ± 0.8; women: 259.7 ± 0.7) (P = 0.007). After the use of analysis of covariance to adjust for triglyceride and high-density lipoprotein cholesterol, LDL size was still significantly lower in diabetic women than in nondiabetic women. In men, however, diabetes was no longer significantly associated with LDL size after similar adjustments. Fasting glucose was more strongly correlated with LDL size in women (r = −0.30) than in men (r = −0.18).

CONCLUSIONS

We conclude that LDL size is significantly lower in diabetic subjects of both sexes than in nondiabetic subjects, but that diabetic dyslipidemia accounts for the association in diabetic men. The stronger association between LDL size and diabetes in women than in men may partially explain the greater relative risk of CHD observed in women with NIDDM in some studies.
Incidence of Type I Diabetes in the Liguria Region, Italy: Results of a prospective study in a 0- to 14-year age-group
Authors: Mazzella Massimo , Cotellessa Mario , Bonassi Stefano , Mulas Roberta , Caratozzolo Antonino , Gaber Shamir , Romano Cesare
Published: March 2007

OBJECTIVE

To assess updated incidence of insulin-dependent diabetes mellitus (IDDM) in 0- to 14-year-old children in Liguria, a northwest region of Italy.

RESEARCH DESIGN AND METHODS

Incident cases were recorded prospectively from 1987 to 1991. Incidence rates (IRs) were directly standardized on the basis of the 1990 world population. The independent effect of age, sex, residence, and calendar year was estimated with a Poisson regression model. The degree of ascertainment was calculated in accordance with the capture/recapture method.

RESULTS

During 5 full calendar years, 117 new cases of IDDM in children were diagnosed in Liguria. The standardized IR over the 5-year period was 11.72 cases·100,000−1·year−1. The sex-specific IR among males and females was 11.45 and 12.01, respectively. The age-specific IR was higher in the 5–9 age-group.

CONCLUSIONS

The IR of IDDM in Liguria is among the highest in southern Europe and approaches that of northern European countries. In particular, it is much higher than those reported in the surrounding Italian regions, except for Sardinia. Therefore, the geographical distribution of IDDM does not seem to reflect the simple north-south gradient reported in several previous studies.
Effect of Fosinopril on Cardiac and Metabolic Parameters in Patients With NIDDM
Authors: Holdaway Ian M , Gamble Greg D , Sanders Gillian A , Greaves Sally C , Ellis-Pegler Elaine M , Sharpe Norman
Published: March 2007

OBJECTIVE

To determine whether the angiotensin-converting enzyme (ACE) inhibitor fosinopril can favorably alter cardiac function in non-insulin-dependent diabetes mellitus NIDDM) patients who have either normal blood pressure (BP) or mild, untreated hypertension.

RESEARCH DESIGN AND METHODS

Fifty-five NIDDM subjects with normal BP or mild, untreated hypertension were randomized to treatment with the ACE-inhibitor fosinopril or placebo for 6 months in a randomized, double-blind trial to determine the effect of fosinopril on echocardiographic measurements.

RESULTS

Left ventricular mass index (LVMI) fell by 6.5 ± 4.7% (mean ± SD) with fosinopril and increased by 8.6 ± 3.5% during placebo treatment (P < 0.02), and isovolumic relaxation time improved significantly in those with elevated baseline levels (P = 0.02). Systolic BP fell significantly, but this did not correlate with the change in LVMI, suggesting a possible direct action of fosinopril on the heart.

CONCLUSIONS

Fosinopril appears to have significant cardiac benefits in patients with NIDDM who have normal or mildly elevated BP. These benefits are achieved without adversely affecting renal status and without impairing metabolic control of diabetes.
Enhanced Pressor Responsiveness to Norepinephrine in Type II Diabetes: Effect of ACE inhibition
Authors: Ciavarella Adolfo , Mustacchio Anna , Ricci Chistina , Capelli Maurizio , Vannini Pietro
Published: March 2007

OBJECTIVE

To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on the pressor responsiveness to norepinephrine in type II diabetes.

RESEARCH DESIGN AND METHODS

Eight normotensive subjects, eight mild-to-moderate hypertensive type II diabetic patients, and eight nondiabetic patients with essential hypertension were studied before and after 4 weeks of being administered enalapril. The pressor response to norepinephrine was assessed by infusing the hormone in an antecubital vein at incremental doses of 30 ng·kg−1 · min−1 for periods of 5 min until reaching an increase of 20 ± 2 mmHg in mean arterial pressure (MAP) measured by an automatic device at 1-min intervals. An effective dosage of norepinephrine that increased MAP by 20 mmHg (EDNE 20) was thereafter calculated. Before and during the last minute of norepinephrine infusion at maximum dosage, a venous blood sample was drawn to determine plasma renin activity (PRA), aldosterone, and norepinephrine levels.

RESULTS

In the three groups of patients, blood pressure and aldosterone were reduced while PRA was raised following ACE inhibition. Basal and maximum postinfusion levels of norepinephrine were not modified by enalapril. The EDNE 20 was basally lower in diabetic patients and remained unchanged after ACE inhibition, contrary to that observed in nondiabetic patients with essential hypertension.

CONCLUSIONS

Both normotensive and hypertensive type II diabetic patients have an increased pressor responsiveness to norepinephrine that is not modified by therapeutic doses of enalapril, contrary to what is observed in nondiabetic patients with essential hypertension.
Serum Sialic Acid, a Risk Factor for Cardiovascular Disease, Is Increased in IDDM Patients With Microalbuminuria and Clinical Proteinuria
Authors: Crook Martin A , Earle Kenneth , Morocutti Anna , Yip Jeannie , Viberti Giancarlo , Pickup John C
Published: March 2007

OBJECTIVE

An elevated serum sialic acid concentration has recently beenshown to be a potent cardiovascular risk factor in the general population. Because clinical proteinuria is associated with a high frequency of cardiovascular disease, and because microalbuminuria predicts the development of renal and cardiovascular disease in diabetes, we investigated whether serum sialic acid levels are increased in insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria or clinical proteinuria.

RESEARCH DESIGN AND METHODS

We studied 23 patients with IDDM who had a normal urinary albumin excretion rate, 23 patients who had microalbuminuria, and 23 patients with clinical proteinuria. The patients were matched for age, sex, duration of diabetes, GHb levels, and body mass index (BMI). Fasting blood samples were taken for measurement of sialic acid, cholesterol, triglyceride, creatinine, and GHb.

RESULTS

Serum sialic acid was significantly higher in the microalbuminuric patients compared with the normoalbuminuric group (mean ± SD: 1.93 ± 0.26 vs. 1.76 ± 0.27 mM, P < 0.01). Moreover, serum sialic acid was also significantly higher in the group with clinical proteinuria compared with the microalbuminuric patients (2.34 ± 0.24 vs. 1.93 ± 0.26 mM, P < 0.001). Serum sialic acid was not related independently to age, BMI, diabetes duration, GHb, blood pressure, serum cholesterol, triglyceride, or creatinine concentration in any of the diabetic groups.

CONCLUSIONS

These observations suggest that the serum sialic acid concentration is raised in IDDM patients with both microalbuminuria and clinicalproteinuria and may play a role as a cardiovascular risk factor or disease marker in these conditions.
Evaluation of the Costs to Medicare of Covering Therapeutic Shoes for Diabetic Patients
Authors: Wooldridge Judith , Moreno Lorenzo
Published: March 2007

OBJECTIVE

A three-year demonstration was fielded in three states to evaluate the cost to Medicare of a therapeutic shoes benefit for Medicare Part B beneficiaries with severe diabetic foot disease.

RESEARCH DESIGN AND METHODS

Eligible Medicare beneficiaries who applied were randomly assigned to either a treatment group that received the extra therapeutic shoe coverage or a control group that received only standard Medicare coverage. This study analyzes the Medicare payments and service use of 3,428 demonstration participants in California, Florida, and New York for whom data on a 12-month follow-up period were available. These results are comparable to those for the entire sample over a variable length follow-up period that averaged 20 months but ranged from 3 months to 3 years.

RESULTS

Differences between groups are not statistically significant. However, Medicare payments for all services among the treatment group were $451 (3.8%) higher than those for all services among the control group. Similarly, Medicare payments for foot-care services were $318 (14.6%) higher among beneficiaries in the treatment group, which considerably exceeded the cost of the shoe benefit ($118).

CONCLUSIONS

The demonstration produced no definitive evidence that expanding Medicare Part B to cover therapeutic shoes for beneficiaries with severe diabetic foot disease would increase total Medicare costs. However, our findings indicate that the demonstration was successful at increasing therapeutic shoe ownership and was instrumental in increasing beneficiaries' use of the shoes when walking outdoors.
The Prediction of Diabetic Neuropathic Plantar Foot Ulceration by Liquid-Crystal Contact Thermography
Authors: Benbow Susan J , Chan Ah W , Bowsher David R , Williams Gareth , Macfarlane Ian A
Published: March 2007

OBJECTIVE

To assess whether the development of plantar foot ulceration could be predicted from the mean plantar foot temperature (MFT), as assessed by liquid-crystal contact thermography (LCT), in patients with peripheral neuropathy.

RESEARCH DESIGN AND METHODS

Fifty patients with painful diabetic sensorimotor neuropathy were studied prospectively. Initially, 30 patients had no significant peripheral vascular disease (PVD) (ankle:brachial systolic blood pressure ratio >1.0). LCT was used to assess the MFT from eight standard plantar sites.

RESULTS

Initial MFT was higher in the patients without PVD (28.2 ± 2.9°C, mean ± SD) than in patients with PVD (25.6 ± 1.9°C, P < 0.001) and in nondiabetic control subjects (25.7 ± 2.1°C, P < 0.001). At review, on average 3.6 (range 3.0–4.1) years later, 11 patients had died (6 of whom had PVD), and one was lost to follow-up. Six patients (seven feet) from the group without PVD had developed neuropathic plantar foot ulcers. The initial MFT was significantly higher in these seven feet (30.5 ± 2.6°C) than in the 38 feet of the 19 survivors in this group (27.8 ± 2.3°C, P < 0.01). Only one patient with PVD developed a plantar ulcer, although four required foot surgery for ischemie feet.

CONCLUSIONS

LCT is a simple, inexpensive, and noninvasive method of identifying the neuropathic foot at increased risk of ulceration. Patients with high plantar foot temperatures are at increased risk of neuropathic foot ulceration. A normal or low MFT in the neuropathic foot is a marker of PVD, which confers an increased risk of ischemie foot disease.
Feasibility of Insulin-Glucose Infusion in Diabetic Patients With Acute Myocardial Infarction: A report from the multicenter trial: DIGAMI
Authors: Malmberg Klas A , Efendic Suad , Rydén Lars E ,   For The Multicenter Study Group
Published: March 2007

OBJECTIVE

To investigate the effect of insulin-glucose infusion on metabolic control and hypoglycemie episodes and its feasibility and safety in patients with diabetes and myocardial infarction (MI) compared with conventional treatment.

RESEARCH DESIGN AND METHODS

Of 327 patients with suspected acute MI, 158 were randomized to insulin-glucose infusion for at least 24 h and 169 received conventional therapy. We determined the 24-h blood glucose profile in the infusion group, the degree of metabolic control, hypoglycemie events, and in-hospital complications within the two study groups.

RESULTS

Blood glucose fell from 14.6 ± 2.9 to 9.2 ± 2.9 mM during the first 24 h in patients receiving insulin-glucose and from 15.8 ± 4.3 to 12.0 ± 4.4 mM in control patients (P < 0.01). Serum potassium decreased 0.21 ± 0.56 mM in the infusion group (P < 0.001) and 0.11 ± 0.59 mM in the control group (P < 0.05). The difference between the groups was not significant. Twenty-eight of the 158 patients developed an episode of hypoglycemia (blood glucose < 3.0 mM) during the insulin-glucose infusion. There were no significant differences in the number of episodes of ventricular tachyarrhythmias or in ischemie events between patients with and without hypoglycemia.

CONCLUSIONS

The protocol outlined in this study gives more rapid and better metabolic control than does conventional treatment. This treatment seems to be a feasible alternative for clinical attempts. Before it can be recommended for general use, the impact on mortality needs to be evaluated.
Assessment of the DQB1-DQA1 Complete Genotype Allows Best Prediction for IDDM
Authors: Tosi Giovanna , Facchin Alberto , Pinelli Leonardo , Accolla Roberto S
Published: March 2007

OBJECTIVE

To analyze the HLA-DQ (human leukocyte antigen) genetic association with insulin-dependent diabetes mellitus (IDDM) patients of the Northeast Italian population.

RESEARCH DESIGN AND METHODS

Fifty-one IDDM patients and 52 healthy control subjects were molecularly typed for DQB1 and DQA1 loci by using allele-specific oligonucleotide probes and polymerase chain reaction amplified genomie DNA. DNA enzyme immunoassay was used to assess allele specificities.

RESULTS

IDDM status strongly correlated with DQB1 alleles carrying a non-aspartic acid (non-Asp) residue in position 57 of DQα-chain and DQA1 alleles with an arginine (Arg) residue in position 52 of DQa-chain. Individuals with two DQB1 (non-Asp) alíeles and two DQAl(Arg) alleles had the highest relative risk for disease: they constituted ∼40% of IDDM patients compared with 0% of control subjects. Heterozy-gosis at either residue 57 of DQB1 or residue 52 of DQA1 was sufficient to abrogate statistical significance for disease association, although 47% of IDDM patients were included in these two groups compared with 21% of normal control subjects. On the other hand, the presence of two DQB1 alleles with Asp in position 57 was sufficient to confer resistance to disease irrespective of the DQA1 genotype.

CONCLUSIONS

The results demonstrate that the complete HLA-DQ genotype, more than a single DQB1 or DQA1 locus, should be determined to estimate the highest risk for disease. Screening a population for preventive purposes and/or early signs of IDDM should then take advantage of this result, and “susceptible homozygous” individuals should be followed very closely and considered the first group of choice for possible new therapeutic trials.
Epidemiology of IDDM in Switzerland: Increasing incidence rate and rural-urban differences in Swiss men born 1948-1972
Authors: Schoenle Eugen J , Molinari Luciano , Bagot Michael , Semadeni Sandra , Wiesendanger Monika
Published: March 2007

OBJECTIVE

To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in Switzerland by undertaking a retrospective analysis of the registry of the Swiss army, which contains updated medical files for all male Swiss citizens. Nationwide data for IDDM epidemiology have not been available in Switzerland.

RESEARCH DESIGN AND METHODS

Every male Swiss citizen is obliged to enlist in the Swiss military service at 19 years of age, when a personal, continuously updated medical file is established. Diabetes is an exclusion condition for military service and is clearly marked in the file. A total number of 514,747 files, corresponding to birth year cohorts 1948-1950, 1955-1957, 1962-1964, and 1970-1972, have been manually checked for the diagnosis of IDDM.

RESULTS

IDDM was identified in 926 cases in the four groups of three age-cohorts. The incidence at ≤15 years (per 100,000/year) was 4.5 in the age cohorts 1948-1950 and 7.2 in the age cohorts 1970-1972 (P < 0.005). An additive age-cohort Poisson regression model fits the nationwide incidences adequately, neither a period effect nor age X cohort interactions being required. In the oldest age cohorts, the age-specific incidence of IDDM was calculated up to the age of 43 and was ∼7/ 100,000/year in men between 20 and 40. In these age cohorts, we found an ∼50% higher risk to develop IDDM at age ≤19 for men living in an urban region and a significantly (P < 0.005) increased incidence between 20 and 40 years in rural regions compared with urban regions.

CONCLUSIONS

The incidence of IDDM in Switzerland is comparable to other countries in central Europe and has been increasing in the last 20 years. This is in accordance to most recent epidemiological studies worldwide. In addition, the data suggest exogenous factors inducing IDDM at a younger age in urban regions.
Children With Newly Diagnosed IDDM Have Increased Levels of Antibodies to Bovine Serum Albumin But Not to Ovalbumin
Authors: Saukkonen Tero , Savilahti Erkki , Vaarala Outi , Virtala Esa T , Tuomilehto Jaakko , Åkerblom Hans K ,   The Childhood Diabetes in Finland Study Group
Published: March 2007

OBJECTIVE

To study the humoral immune response to bovine serum albumin (BSA) and ovalbumin (OA) in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

We examined serum samples from 505 children 0.8–14.9 years of age with newly diagnosed IDDM for antibodies to BSA and OA by enzyme-linked immunosorbent assay (ELISA). We also had two control groups: 85 unrelated control children (0.8–7.1 years of age) and 395 nondiabetic siblings (3.0–14.9 years of age). The specificity of antibodies detected in ELISA was confirmed by immunoblotting in a subset of sera with varying levels of antibodies.

RESULTS

Diabetic children <7 years of age had a significantly higher level of IgG (immunoglobulin) antibodies to BSA than did unrelated control children (P < 0.0001). The difference was greatest in the youngest group of children, 0.8–2.9 years of age. IgA antibodies to BSA were detected more frequently among diabetic than control children (P = 0.0009). Levels of IgG and IgA antibodies to ovalbumin did not differ between diabetic and control children. Diabetic children 3.0–14.9 years of age also had higher levels of IgG and IgA antibodies to BSA than did their age- and sex-matched nondiabetic siblings (P = 0.02 and P < 0.0001, respectively). Those siblings who contracted IDDM during the follow-up period (n = 15) had a measurable level of IgA antibodies to BSA more often than did those who remained nondiabetic (60 and 34%, respectively; P = 0.04). Neither before nor after diagnosis of IDDM was there any significant trend in antibody levels.

CONCLUSIONS

A high level of antibodies to BSA commonly associates with IDDM, whereas the humoral immune response to OA is similar in diabetic and nondiabetic children.
Fibrinolysis and Diabetic Retinopathy in NIDDM
Authors: Mansfield Michael W , Grant Peter J
Published: March 2007

OBJECTIVE

By contributing to a prothrombotic state, increased levels of plasminogen activator inhibitor-1 (PAI-1) may be involved in the pathogenesis of the vascular complications of non-insulin-dependent diabetes mellitus (NIDDM). The objective of this study was to compare levels of components of the fibrinolytic system in NIDDM subjects with and without retinopathy.

RESEARCH DESIGN AND METHODS

A total of 135 Caucasian NIDDM subjects treated with oral therapy or diet alone were classified by the presence or absence of retinopathy, and fasting blood samples were taken for assay of PAI-1 antigen and activity, tissue plasminogen activator (t-PA), t-PA complexed with PAI-1, euglobulin clot lysis time (a measure of overall fibrinolytic activity), glucose, HbA1c, cholesterol, triglyceride, and insulin levels.

RESULTS

Subjects with retinopathy had a longer disease duration than those without (9 vs. 5 years, P < 0.0001) and had lower levels of PAI-1 (PAI-1 antigen) (geometric mean and 95% confidence interval), 13.9 (10.4–18.6) vs. 24.1 (21.2–27.4) ng/ml (P < 0.0005); t-PA antigen, 9.6 (8.6–10.7) vs. 11.5 (10.8-12.3) ng/ml (P < 0.01); t-PA—PAI-1 complexes, 6.2 (5.2–7.2) vs. 7.8 (6.8–8.8) ng/ml (P < 0.05); and insulin, 11.5 (9.3-14.3) vs. 19.5 (17.0–22.3) mU/l (P < 0.0005). Euglobulin clot lysis time was shorter in the subjects with retinopathy, 273 (238–312) vs. 327 (303–352) min. When entered into a logistic regression model, disease duration, PAI-1 antigen, and HbA1c remained as significant independent associates of the presence of retinopathy.

CONCLUSIONS

These results do not support the hypothesis that impaired fibrinolysis due to elevated PAI-1 is associated with the development of retinopathy because fibrinolysis is indeed enhanced and PAI-1 lower in subjects with retinopathy.
Maternal Metabolic Control and Risk of Microcephaly Among Infants of Diabetic Mothers
Authors: Greene Michael F , Allred Elizabeth N , Leviton Alan
Published: March 2007

OBJECTIVE

To measure the incidence of microcephaly among infants of diabetic mothers (IDM) and assess its relationship to metabolic control during pregnancy.

RESEARCH DESIGN AND METHODS

Head circumference data for 556 consecutive live-born singleton infants of women with insulin-requiring diabetes antedating pregnancy delivered between 28 and 40 weeks of gestation and the results of 3,242 HbA1 determinations collected during their pregnancies were examined.

RESULTS

There were fewer head circumferences at or below the 3rd percentne and more at or above the 97th percentik than expected. Head circumference was not related to maternal metabolic control as documented by the HbA1 values.

CONCLUSIONS

The less-than-expected incidence of microcephaly observed in this patient population probably reflects the well-known tendency of IDM toward macrosomia.
Impaired Glucose Tolerance Leads to Delayed Diagnosis of AlstrÖm Syndrome
Authors: Holder Martin , Hecker Wolfgang , Gilli Guilio
Published: March 2007

OBJECTIVE

To emphasis the need for timely diagnosis of AlstrÖm syndrome.

CASE

We report a case of late-detected AlstrÖm syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia.

RESULTS

Diagnosis was made and the patient's impaired glucose tolerance improved by diet.

CONCLUSIONS

Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.
A Comparison of Premixed Insulin Preparations in Elderly Patients: Efficacy of 70/30 and 50/50 human insulin mixtures
Authors: Brodows Robert , Chessor Ruth
Published: March 2007

OBJECTIVE

To compare the postprandial hyperglycemic response to a standard breakfast of two premixed humulin insulin mixtures, 50/50 (50% NPH human insulin and 50% regular human insulin) and 70/30 (70% NPH human insulin and 30% regular human insulin) in elderly non-insulin-dependent diabetes mellitus (NIDDM) patients.

RESEARCH DESIGN AND METHODS

On two mornings, each patient (n = 20) consumed a standard breakfast after a single dose of 50/50 or 70/30 insulin (0.3 U/kg) was administered in a randomized crossover fashion. Plasma glucose and serum free insulin concentrations were measured before and for 4 h after insulin administration.

RESULTS

Plasma glucose reached a peak at 60 min and a nadir at 240 min for both types of insulin. No differences in maximum and minimum glucose concentrations, time to maximum and minimum glucose concentrations, or areas under the curve were noted. Free insulin levels did not differ significantly.

CONCLUSIONS

These results suggest that small changes in the composition of premixed insulin mixtures in NIDDM patients may not result in improved postprandial glycemic control.
Serial Changes in the Prevalence of Islet Cell Antibodies and Islet Cell Antibody Titer in Children With IDDM of Abrupt or Slow Onset
Authors: Urakami Tatsuhiko , Miyamoto Yukinobu , Matsunaga Hiroko , Owada Misao , Kitagawa Teruo
Published: March 2007

OBJECTIVE

To elucidate the significance of clinical and immunogenic heterogeneity in Japanese children with insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

Serial changes in the prevalence of islet cell antibodies (ICAs) and in ICA titer were monitored for 10 years after diagnosis in 34 IDDM children, 17 with abrupt onset and 17 with slow onset, whose durations of disease were > 5 years.

RESULTS

In slow-onset IDDM children, enough β-cell function was maintained in the early phase of the disease within 2 years after diagnosis. There was a high prevalence of ICAs in children with both forms of IDDM at the time of diagnosis (abrupt onset 94% slow onset 82%). However, the decline in the frequency of ICAs in slow-onset IDDM seemed less marked than in abrupt-onset IDDM after a duration of ≥ 1 year (47 vs. 82%, 1–3 years; 24 vs. 47%, 3–5 years; 24 vs. 47%, 5–7 years; 18 vs. 53%, 7–10 years, P < 0.05). In terms of changes in ICA titer, abrupt-onset IDDM children initially had high ICA levels of 160–320 Juvenile Diabetes Foundation units (JDF U), but these titers decreased rapidly after the 1st year. On the other hand, slow-onset IDDM children tended to continue to be ICA+ for a relatively long period with low titers of 20–40 JDF U. Among 12 children who remained ICA+ for > 5 years, slow onset was noted in 67% while abrupt onset was seen in only 33%.

CONCLUSIONS

From these results, we speculated that changes in ICA titer reflect the slow autoimmune destruction of pancreatic β-cells. It may be probable that immunogenic factors as well as environmental factors could affect the clinical features in the early phase of IDDM in children.
Severe Islet Amyloidosis in Congenital Generalized Lipodystrophy
Authors: Garg Abhimanyu , Chandalia Manisha , Vuitch Frank
Published: March 2007

OBJECTIVE

Islet amyloidosis may be one mechanism for pancreatic islet β-cell loss that is associated with the development of NIDDM. However, the question remains whether chronic overstimulation of insulin and islet amyloid polypeptide (IAPP) secretion in states of insulin resistance could lead to formation of islet amyloidosis and hence NIDDM in some patients. We studied pancreatic islet pathology in congenital generalized lipodystrophy, a genetic syndrome of extreme insulin resistance that may provide some clues.

RESEARCH DESIGN AND METHODS

Our patient was a 24-year-old African-American woman with congenital generalized lipodystrophy. Severe acanthosis nigricans was noted in her since age 6. At ages 12 and 16, normal and impaired glucose tolerances, respectively, were noted on oral glucose tolerance tests but were accompanied by extreme fasting and post-prandial hyperinsulnemia. Overt diabetes developed at age 18 and she required ∼180 U of insulin daily. Immediately after an accidental death at age 24, an autopsy was performed. Pancreatic histology was studied in detail using routine methods and immunohistochemical techniques.

RESULTS

Some scarring of the pancreas as a result of previous episodes of acute pancreatitis was observed. Severe amyloidosis was noted in 89% of the islets, sparing those that were rich in pancreatic polypeptide-secreting cells. Amyloid deposits stained intensely on immunostaining with antibodies against amylin. Marked paucity of β-cells was evident. The ratio of β- to α-cells was reduced to 1:1 (normal ratio ∼ 4:1).

CONCLUSIONS

These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as β-cell atrophy.
The Effects of High- and Medium-Dose Metformin Therapy on Cardiovascular Risk Factors in Patients With Type II Diabetes
Authors: Grant Peter J
Published: March 2007

OBJECTIVE

To study the dose response to metformin in type II diabetic patients.

RESEARCH DESIGN AND METHODS

Type II diabetic patients with a BMI > 25 were treated with 3,000 mg/day (n = 27), 1,500 mg/day (n = 25), or placebo (n = 23) for 6 months. Venous blood samples were taken at each visit for plasma glucose and insulin, HbA1c, triglyceride and cholesterol, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (TPA), and euglobulin clot lysis time (ECLT). Blood pressure was recorded at each visit.

RESULTS

There were no changes in BMI or blood pressure. Blood glucose fell (mean) by 3.6 mmol/l in the high-dose and 0.5 mmol/l in the low-dose group over the 6-month study (P < 0.001 and NS compared with placebo). HbA1c and plasma insulin fell in both treatment groups (HbA1c, P < 0.001; insulin, P < 0.003 and 0.03). There was a fall in triglyceride (P < 0.05) and cholesterol (P < 0.008) with high-dose metformin. PAI-1 antigen and activity fell by ∼ 20% of baseline in both treatment groups (PAI-1 antigen high dose, P < 0.01; PAI-1 antigen low dose, P < 0.002: PAI-1 activity high and low dose, P < 0.003). There were significant falls in total tPA in both groups (P < 0.004), but the overall effect was a fall in ECLT (P < 0.03).

CONCLUSIONS

The results indicate that metformin has favorable effects on cardiovascular risk factors associated with type II diabetes. The effects on glycemic control and lipids are dose-dependent, while the enhanced fibrinolytic response is independent of the doses used.
Elevated Plasma Levels of Transforming Growth Factor-β1 in NIDDM
Authors: Pfeiffer Andreas , Middelberg-Bisping Kristina , Drewes Cordula , Schatz Helmut
Published: March 2007

OBJECTIVE

Transforming growth factor-β (TGF-β) is a potent inducer of extracellular matrix production and of fibrogenesis and has been associated with the occurrence of diabetic micro- and macrovascular complications. Our aim was to determine whether circulating levels of TGF-β1 are altered in NIDDM and, if so, whether they are correlated with blood glucose and show an association with diabetic complications.

RESEARCH DESIGN AND METHODS

Plasma levels of TGF-β1 were determined by enzyme-linked immunosorbent assay in 44 NIDDM patients and 28 control subjects of comparable age and weight and were correlated with parameters of metabolic control and the occurrence of micro- and macrovascular complications.

RESULTS

TGF-β1 was significantly elevated in NIDDM (7.9 ± 1.0 ng/ml), as compared with control subjects (3.1 ± 0.4 ng/ml, P < 0.001) and correlated with glycosylated hemoglobin (r2 = 0.42; P < 0.001). Thrombocyte levels of TGF-β1 were similar in control subjects (54 ± 7 pg/ml, n = 16) and diabetic patients (61.6 ± 18 pg/ml, n = 13; P = 0.357). Elevated TGF-β1 levels were associated with retinopathy and neuropathy.

CONCLUSIONS

We conclude that plasma levels of TGF-β1 are elevated in NIDDM patients and may be related to average blood glucose. Preliminary data suggest that they may contribute to the occurrence of diabetic complications.
Persistent Activation of CD8+ T-cells Characterizes Prediabetic Twins
Authors: Peakman Mark , Leslie R David G , Alviggi Lorenzo , Hawa Mohammed , Vergani Diego
Published: March 2007

OBJECTIVE

Elevated circulating levels of activated CD3+ T-cells are characteristic of type I diabetes at diagnosis, and activated CD8+ (cytotoxic/suppressor) T-cells predominate in the islet infiltrate. The aim of this study was to examine the peripheral blood of prediabetic and nondiabetic identical twins of patients with type I diabetes for the presence of activated CD8+ T-cells and by comparing these groups, analyze the relationship of such cells to the development of the disease.

RESEARCH DESIGN AND METHODS

In a 10-year prospective study, blood T-cell subsets (CD3+ total T-cells, CD4+ helper/inducer, and CD8+ cytotoxic/suppressor) were analyzed for evidence of activation (cell surface expression of HLA-DR, CD25) in 18 identical twins of patients with type I diabetes, 8 of whom became diabetic (prediabetic twins), while 10 remained nondiabetic after at least 8 years of follow-up and are now at low risk for type I diabetes. Fifteen healthy individuals were studied as control subjects.

RESULTS

At the beginning and during the study, percentage levels of activated CD3+ HLA-DR+ T-cells were significantly elevated in prediabetic and low-risk twins compared with control subjects (P < 0.005) but remained high only in prediabetic twins (P < 0.005). Both prediabetic and low-risk twins had elevated levels of HLA-DR+ CD4+ T helper cells compared with control subjects throughout the study (P < 0.001), and these remained high in both (P < 0.001 and P < 0.05, respectively). Only prediabetic twins had elevated levels of HLA-DR+ CD8+ T-cells during the study. These were significantly higher than in control subjects (P < 0.005) and low-risk twins (P < 0.05) and remained persistently elevated to diagnosis (P < 0.001). Abnormally elevated levels of HLA-DR+ CD8+ T-cells in twins indicate a 50% risk of progression to type I diabetes by life-table analysis (P = 0.01), with a positive predictive value of 100%, sensitivity of 50%, and specificity of 100%. Elevated CD25+ T-cell levels in prediabetic and low-risk twins were less marked and less able to discriminate between the twin groups.

CONCLUSIONS

These results demonstrate that prediabetes is characterized by persistent elevation of HLA-DR+ CD8+ T-cells with the same cytotoxic phenotype as cells predominating in the islet at diagnosis, suggesting that the circulating cells may have a role in the pathogenesis of islet damage.
Acute Effects of Intraperitoneal Versus Subcutaneous Insulin Delivery on Glucose Homeostasis in Patients With NIDDM
Authors: Kelley David E , Henry Robert R , Edelman Steven V ,   The Veterans Affairs Implantable Insulin Pump Study Group
Published: March 2007

OBJECTIVE

The objective of this study is to compare the effect of intraperitoneal versus subcutaneous insulin injection on hepatic glucose production (HGP) and systemic glucose utilization (Rd) in patients with NIDDM.

RESEARCH DESIGN AND METHODS

Eight male volunteers with NIDDM, each of whom had a programmable-rate, implantable insulin pump, were given an injection of insulin (0.15 units/kg body wt) by intraperitoneal or subcutaneous injection on separate days in randomized order. Plasma glucose was kept constant for 5 h using the glucose clamp technique, and HGP and Rd were measured using isotope dilution.

RESULTS

Intraperitoneal insulin injection resulted in higher and earlier peak systemic insulin concentrations (1,469 ± 245 vs. 454 ± 48 pmol/l, P < 0.01). Glucose Rd doubled within 1 h after intraperitoneal injection and was greater than that attained with subcutaneous injection (3.91 ± 0.27 vs. 2.60 ± 0.19 mg · kg−1 · min−1, P < 0.01). Intraperitoneal and subcutaneous injections suppressed HGP and plasma free fatty acid to a similar extent during the first 3 h, effects that persisted through 5 h after subcutaneous insulin injection but waned 3–4 h after intraperitoneal injection.

CONCLUSIONS

In patients with NIDDM, intraperitoneal insulin injection achieves more rapid and greater peak values for stimulation of glucose Rd than subcutaneous insulin injection. With regard to HGP and lipolysis, intraperitoneal and subcutaneous injections achieve similar initial suppression but this is maintained for a more limited duration with intraperitoneal as compared with subcutaneous injection. These differences in insulin action seem directly related to the rapidity of insulin absorption with intraperitoneal injection.
Feasibility and Effectiveness of Peripheral Percutaneous Transluminal Balloon Angioplasty in Diabetic Subjects With Foot Ulcers
Authors: Faglia Ezio , Favales Fabrizio , Quarantiello Anthonella , Calia Patrizia , Brambilla Giorgio , Rampoldi Antonio , Morabito Alberto
Published: March 2007

OBJECTIVE

The aim of this study was to evaluate the feasibility and effectiveness of this vascular procedure in diabetic inpatients with foot ulcers.

RESEARCH DESIGN AND METHODS

In 80 consecutive inpatient diabetic subjects with a foot ulcer, an angiographic study of the lower limbs was carried out to evaluate the necessity and possibility of performing vascular procedures. In 22 subjects, vascular procedure was not necessary; in 26 subjects, peripheral transluminal angioplasty was carried out; in 10 subjects, angioplasty was considered impossible and a peripheral bypass graft was performed; and in 22 subjects, no vascular procedure was considered possible.

RESULTS

Of the 26 angioplasties, 8 were performed in iliac or femoral arteries and 18 were performed in the popliteal artery and its branches. The angioplasty was considered unsuccessful in 4 subjects and successful in 22. After angioplasty, on discharge, parameters of limb perfusion improved significantly: transcutaneous oxygen tension was 27.0 ± 14 mm/Hg on admission and 44.6 ± 14 mm/Hg on discharge (P < 0.001); ankle-brachial index was 0.61 ± 0.23 on admission and 0.77 ± 0.20 on discharge (P = 0.018). Of 22 subjects who underwent successful angioplasty, 21 ended the follow-up of 12 months: during this period, they showed no relapses in the salvaged limb, and their parameters of limb perfusion did not significantly vary.

CONCLUSIONS

Angioplasty is feasible in a large percentage of diabetic subjects with peripheral occlusive arterial disease and foot ulcer and is often also practicable in the popliteal artery and its branches. In these subjects, angioplasty significantly improves the parameters of limb perfusion. Angioplasty is therefore an important therapeutic tool in ulcerated diabetic foot care.
Meta-Analysis of Nicotinamide Treatment in Patients With Recent-Onset IDDM
Authors: Pozzilli Paolo , Browne Peter D , Kolb Hubert ,   The Nicotinamide Trialists
Published: March 2007

OBJECTIVE

Nicotinamide, a vitamin of the B group, has in vitro actions capable of interfering with the pathogenetic process leading to IDDM. Since 1987, several studies have evaluated nicotinamide as a means of protecting β-cells from end-stage destruction in insulin-treated patients with newly diagnosed IDDM. The aim of the study was to determine whether nicotinamide protects residual β-cell function when given at IDDM diagnosis.

RESEARCH DESIGN AND METHODS

We performed a meta-analysis of the integrated parameters of metabolic control (C-peptide, glycosylated hemoglobin, insulin dose) in 10 randomized (5 of which were placebo) controlled trials conducted in recent-onset IDDM patients for a total of 211 nicotinamide-treated patients. Data on the adverse effects of nicotinamide were also collected from an additional four trials to yield a grand total of 291 nicotinamide-receiving patients.

RESULTS

One year after diagnosis, baseline C-peptide was significantly higher in nicotinamide-treated patients, compared with control patients (0.73 ± 0.65 vs. 0.32 ± 0.56 ng/ml, P < 0.005). This statistical difference remained also when the five placebo-controlled trials only were considered (P < 0.05). No differences were observed in the insulin dose required or glycosylated hemoglobin values between nicotinamide and control patients. Adverse effects were reported in few patients (transient elevation of transaminase, n = 2; skin rash, n = 2; recurrent hypoglycemia, n = 2).

CONCLUSIONS

This combined analysis demonstrates a therapeutic effect of nicotinamide in preserving residual β-cell function when given at IDDM diagnosis in addition to insulin. Since adverse effects were negligible, we suggest that prolonged use of nicotinamide after IDDM diagnosis should be tested to see whether residual β-cell function can be preserved for longer periods.
Separate Associations Between Visceral and Subcutaneous Adipose Tissue Distribution, Insulin and Glucose Levels in Obese Women
Authors: Ross R , Fortier L , Hudson R
Published: March 2007

OBJECTIVE

The primary purpose of this study was to determine the separate associations between visceral (VAT) and subcutaneous adipose tissue (SAT) distribution, skeletal muscle (SM), and plasma insulin and glucose levels, and. A second objective was to determine whether anthropometric methods could be used to identify those women who are at increased metabolic risk.

RESEARCH DESIGN AND METHODS

Whole-body SAT, SM, and VAT volume were measured (in liters), using a multislice magnetic resonance imaging (MRI) protocol in 40 premenopausal obese women. Plasma insulin and glucose levels were measured after an overnight fast and in response to a 75-g oral glucose tolerance test (OGTT).

RESULTS

With the exception of fasting glucose, VAT was positively correlated with all insulin and glucose variables (P < 0.01). This observation remained true whether VAT was derived from multiple MR images (i.e., VAT volume [in liters]) or from a single MR image (i.e., VAT area [in squared centimeters]). Furthermore, the segmentation of intraperitoneal adipose tissue (portally drained adipose tissue) from VAT did not improve the observed relationships. VAT remained a significant (P < 0.05) correlate of insulin and glucose area after adjusting for either SAT or abdominal SAT (ASAT). SAT, ASAT, and SM volume were not related to any metabolic variable. Waist circumference (WC) was the single strongest anthropometric correlate for fasting insulin and insulin area (P < 0.05). Because it has been reported that disturbances in insulin-glucose homeostasis are more likely associated with a WC value > 1 m, in subjects matched for total adiposity, we compared the glucose and insulin area values for those with a WC above (n = 17) and below (n = 15) this value. The group with a WC > 1 m had significantly higher values for both insulin and glucose areas (P < 0.05).

CONCLUSIONS

The primary observation is that VAT is associated with plasma insulin and glucose variables independent of whole-body SAT, ASAT, and SM in obese women. In addition, the findings provide support for the utility of WC as an anthropometric tool that may be used to identify a subgroup of obese patients at increased metabolic risk.
The Development of Foot Deformities and Ulcers After Great Toe Amputation in Diabetes
Authors: Quebedeaux Terri L , Lavery Lawrence A , Lavery David C
Published: March 2007

OBJECTIVE

Our aim was to compare the prevalence and severity of foot deformities and the development of ulcerations in patients after a great toe amputations.

RESEARCH DESIGN AND METHODS

We evaluated the presence of deformities of the toes and metatarsophalangeal joints (MTPJs) in patients with a great toe amputation who had an intact unamputated contralateral foot. The contralateral foot served as the patient's own control. We used a binomial test for paired data to compare the presence of deformity and ulcer formation and Fisher's exact test to compare joint flexibility in toes and MTPJs with foot deformities.

RESULTS

There were more deformities of the second (P = 0.012) and third (P = 0.002) toes and lesser MTPJs (P < 0.05) and more rigid deformities of the second (P = 0.002) and third (P = 0.016) toes and second MTPJs (P = 0.035) in feet with great toe amputations. New ulcers were more common in feet that had an amputation (P = 0.002).

CONCLUSIONS

We concluded that amputation of the great toe contributes to the development of deformities of the second and third toes and lesser MTPJs and new ulcer formation in patients with diabetes. When deformities were present, the second and third toes and second MTPJ were more severe in feet with a great toe amputation.
Diminished Thyroxine-Binding Globulin in Pubertal Diabetic Children
Authors: Connors Matthew H , Dunger David B , Chapel Helen , Jefferson Ian , Jowett Terence P , Edwards Philip R
Published: March 2007

OBJECTIVE

To determine the effect of diabetes on thyroid hormone and thyroxine-binding globulin (TBG) concentrations during puberty.

RESEARCH DESIGN AND METHODS

Total thyroxine (TT4), free thyroxine (FT4), and TBG levels of 171 thyroid microsomal antibody-negative subjects with normal thyroid-stimulating hormone (TSH) levels were measured and compared with those of nondiabetic adolescents. A random subset of 68 diabetic patients (40 boys and 28 girls) and 51 control subjects (24 boys and 27 girls) were analyzed for puberty-related changes.

RESULTS

Most TT4 levels of diabetic subjects (80% of girls and 63% of boys) were below the 50th percentile for the normal range. TT4 increased with age in girls (r = 0.25, P < 0.04) but not in boys. FT4 was within normal limits in both sexes. TBG measurements were below the 50th percentile and 20% were below the 95% CI for both sexes; TT4 correlated with TBG in boys (r = 0.54, P < 0.001) and in girls (r = 0.58, P < 0.001). Duration of diabetes had no effect, whereas TT4 and FT4 levels were higher in girls with the lowest HbA1 levels (r = −0.29, P < 0.01 and r = −0.45, P < 0.01). Levels of TBG were reduced for all male pubertal stages (P < 0.01) and for early and late female pubertal stages (P < 0.01). There was no direct relationship between glucose control or the duration of diabetes and levels of TBG.

CONCLUSIONS

Because TT4 levels are low and correlate with the low levels of TBG, it is important to measure free thyroid hormone and TSH levels in diabetic adolescents to establish euthyroidism.