bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic Differences in Correlates of Microalbuminuria in NIDDM: The role of the acute-phase response
Authors: Islam Niaz , Kazmi Fahrat , Chusney Gary D , Mattock Martin B , Zaini A , Pickup John C
Published: March 2007

OBJECTIVE

To investigate whether microalbuminuria is associated with markers of the acute-phase response in NIDDM and whether there are ethnic differences in this association among the three main racial groups in Malaysia.

RESEARCH DESIGN AND METHODS

NIDDM patients of Chinese, Indian, and Malay origin attending a diabetic clinic in Kuala Lumpur, Malaysia, were matched for age, sex, diabetes duration, and glycemic control (n = 34 in each group). Urinary albumin-to-creatinine ratio was measured in an early morning urine sample. Biochemical measurements included markers of the acute-phase response: serum sialic acid, triglyceride, and (lowered) HDL cholesterol.

RESULTS

The frequency of microalbuminuria did not differ among the Chinese, Indian, and Malay patients (44, 41, and 47%, respectively). In Chinese patients, those with microalbuminuria had evidence of an augmented acute-phase response, with higher serum sialic acid and triglyceride and lower HDL cholesterol levels; and urinary albumin-to-creatinine ratio was correlated with serum sialic acid and triglyceride. The acute-phase response markers were not different in Indians, with microalbuminuria being high in even the normoalbuminuric Indians; only the mean arterial blood pressure was correlated with urinary albumin-to-creatinine ratio in the Indians. Malay NIDDM subjects had an association of microalbuminuria with acute-phase markers, but this was weaker than in the Chinese subjects.

CONCLUSIONS

Microalbuminuria is associated with an acute-phase response in Chinese NIDDM patients in Malaysia, as previously found in Caucasian NIDDM subjects. Elevated urinary albumin excretion has different correlates in other racial groups, such as those originating from the Indian subcontinent. The acute-phase response may have an etiological role in microalbuminuria.
Diabetes and Long-Term Risk of Mortality From Coronary and Other Causes in Middle-Aged Swedish Men: A general population study
Authors: Adlerberth Annika M , Rosengren Annika , Wilhelmsen Lars
Published: March 2007

OBJECTIVE

To assess the relation between cardiovascular risk factors and long-term cause-specific mortality risk in middle-aged diabetic men, compared with men without diabetes.

RESEARCH DESIGN AND METHODS

This prospective study analyzes a large random population sample of men over a follow-up of 16 years. At baseline in 1974–1977, 249 men with diabetes and 6,851 men without diabetes, all aged 51–59 years, were identified. There were 2,126 deaths, 724 of which were due to coronary heart disease (CHD) and 1,001 deaths were due to any cardiovascular disease (CVD) cause.

RESULTS

After adjustment for age, serum cholesterol, systolic blood pressure, smoking, BMI, and coronary disease at baseline, the relative risk of dying from any cause was 2.50 (95% CI, 2.11–2.95) in men with diabetes, compared with nondiabetic men, and 2.87 (2.31–3.57) for cardiovascular death. Men with diabetes had no significant excessive risk of dying from cancer or violent causes, but the relative risk of dying from any other noncardiovascular cause was 3.69 (2.55–5.34). Most of these deaths were due to diabetes and its complications. Hypercholesterolemia, smoking, and elevated systolic blood pressure predicted both coronary and allcause mortality in diabetic as well as in nondiabetic men. Men with diabetes and serum cholesterol >7.2 mmol/1 had a risk of dying from coronary disease of 45.3 and from any cause of 76.1 per 1,000 observation-years. In men with diabetes, the relative risk of dying associated with serum cholesterol >7.2 mmol/1, as compared with <5.2 mmol/1, was 1.78 (95% CI, 1.05–3.02). The corresponding risk for nondiabetic men was 1.23 (1.04–1.46), and there was a statistically significant interaction between serum cholesterol and diabetes (P = 0.004).

CONCLUSIONS

In men with diabetes, hypercholesterolemia, smoking, and hypertension predict coronary mortality risk, as well as mortality risk from all causes. Men with both diabetes and hypercholesterolemia have severely compromised survival and should be targeted for intervention aimed at lowering their lipid levels.
An Electronic Case Manager for Diabetes Control
Authors: Meneghini Luigi F , Albisser A Michael , Goldberg Ronald B , Mintz Daniel H
Published: March 2007

OBJECTIVE

To evaluate the usage and safety of an electronic case manager (ECM) system designed to facilitate the task of glycemic control. Sustained improvement in blood glucose control is the proven treatment outcome that will reduce or eliminate the long-term complications of diabetes.

RESEARCH DESIGN AND METHODS

A customized microcomputer system served as the ECM. Located at the clinic, this voice-interactive system required the remote patient to need only a touch-tone telephone. Patients accessed the system to report daily selfmeasured glucose levels or hypoglycemic symptoms together with associated lifestyle events. System beta-testing was in an open-case series (n = 184) in an academic diabetes center with the goal of evaluating the ECM in terms of utilization, frequency of crises, and fiscal matters.

RESULTS

Of the patients, 58% (n = 107) actively used the ECM for their daily diabetes care, accumulating 788 patient-months of follow-up. Over 45,000 telephone calls were received by the ECM during the start-up year. Each call was processed instantly and automatically. Patients benefited from having 24-h access to the ECM. Prevalence of diabetes-related crises (hyperglycemia =400 mg/dl [22 mmol/1] or hypoglycemia <50 mg/dl [2.8 mmol/1]) decreased approximately threefold (P < 0.05), with a concomitant statistically significant decrease in HbA1c of 0.8% at 6 months (n = 45, P = 0.024) and 0.9% at 12 months (n = 30, P = 0.044). The ECM provided 24-h on-line assistance in adjusting daily insulin and/or tablet therapy, automatic generation of standardized medical reports, electronic medical-legal documentation, as well as a marked reduction in the time spent on the phone with patients. Clinic visits in managing complex diabetes were reduced approximately twofold (P < 0.0001), and the effort spent by case managers was estimated.

CONCLUSIONS

Patients with diabetes who accessed the ECM system received timely, cost-effective, and reliable medical intervention. This reduced the incidence of diabetic crises and the need for frequent clinic visits. The ECM empowers case managers to provide safer and superior diabetes care.
Relationship Between Serum 1,5-Anhydroglucitol and Urinary Excretion of N-Acetylalucosaminidase and Albumin Determined at Onset of NIDDM With 3-Year Follow-up
Authors: Yamanouchi Toshikazu , Kawasaki Takahiro , Yoshimura Tomoe , Inoue Tae , Koshibu Eri , Ogata Nobuyuki , Funato Hirono , Akaoka Ieo , Miyashita Hideo
Published: March 2007

OBJECTIVE

This prospective study was designed to elucidate the relationship between the serum level of 1,5-anhydroglucitol (1,5AG) and the urinary excretion of N-acetylglucosaminidase (NAG) and albumin in patients who were in the early stages of diabetes.

RESEARCH DESIGN AND METHODS

A total of 1,062 male nondiabetic subjects with impaired glucose tolerance were monitored for blood glucose level once every 2–3 months, and the values were evaluated. Of these 1,062 subjects, 112 showed a worsening of glycemia during the observation period to the level seen in diabetes. We began to monitor the glycemia and parameters of renal damage in the 112 patients from the onset of diabetes.

RESULTS

The urinary excretion of NAG and albumin were elevated even at the onset of diabetes. The abnormal excretion of NAG and albumin was associated with a change in serum 1,5AG and was quickly reversible when the serum 1,5AG improved. In the 3 years after the onset of diabetes, we obtained at least 18 measurements of one parameter for each patient and calculated the mean. Urinary NAG was found to be significantly correlated with the fasting plasma level of glucose (FPG; r = 0.512, P < 0.0001), the level of HbA1 (r = 0.351, P = 0.001), and the level of 1,5AG (r = −0.790, P < 0.0001). The urinary excretion of albumin was weakly but significantly correlated with levels of FPG (r = 0.383, P < 0.0001) and HbA1 (r = 0.337, P = 0.0001), but it was more strongly correlated with 1,5AG (r = −0.632, P < 0.0001). The level of 1,5AG was significantly correlated with FPG (r = −0.681, P < 0.0001) and HbA1 (r = −0.609, P < 0.0001).

CONCLUSIONS

When the renal damage is not severe, the serum level of 1,5AG appeared to be an indicator of the reversible renal damage caused by hyperglycemia, as well as of the severity of the glycemia itself.
Effects of Perindopril and Carvedilol on Endothelium-Dependent Vascular Functions in Patients With Diabetes and Hypertension
Authors: Giugliano Dario , Marfella Raffaele , Acampora Rita , Giunta Riccardo , Coppola Ludovico , D'Onofrio Felice
Published: March 2007

OBJECTIVE

To compare the effects of the ACE inhibitor perindopril and the β-blocker carvedilol on blood pressure and endothelial functions in N1DDM patients with hypertension.

RESEARCH DESIGN AND METHODS

We conducted a double-blind randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in placebo period preceded the active 12-week treatment with perindopril (4–8 mg daily) or carvedilol (25–50 mg daily). Endothelial functions were assessed by evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological (platelet aggregation, blood viscosity, and blood filterability) responses to an intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide.

RESULTS

Both perindopril and carvedilol significantly reduced mean blood pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent; blood filterability remained unchanged in both perindopril- and carvedilol-treated groups. Carvedilol reduced platelet aggregation and blood viscosity significantly (P < 0.05) but perindopril did not. Before treatment, the hemodynamic and rheologic responses to L-arginine were significantly lower in patients (P < 0.05–0.01) than in 20 nondiabetic nonhypertensive control subjects. After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L-arginine. Platelet aggregation response to L-arginine was ameliorated by carvedilol and remained unchanged in the perindopril group.

CONCLUSIONS

At the doses used, both drugs effectively reduce blood pressure and normalize the hemodynamic responses to L-arginine. The implications of the ameliorated endothelial function for the poor cardiovascular outlook of the NIDDM hypertensive patient need further assessment.
Beneficial Effect on Average Lipid Levels From Energy Restriction and Fat Loss in Obese Individuals With or Without Type 2 Diabetes
Authors: Markovic Tania P , Campbell Lesley V , Balasubramanian Santhira , Jenkins Arthur B , Fleury Adriana C , Simons Leon A , Chisholm Donald J
Published: March 2007

OBJECTIVE

The risk of cardiovascular disease in type 2 diabetes is greater than is accounted for by conventional risk factors. We investigated whether energy restriction or modest fat loss improved the lipid profile in obese subjects with and without type 2 diabetes. The relationship of site of adipose tissue loss to lipid changes was also examined.

RESEARCH DESIGN AND METHODS

Lipid levels were measured in 18 subjects with normal glucose tolerance (NGT) (n = 9, BM1 = 31.5 ± 0.8 [SEM] kg/m2) or type 2 diabetes (n = 9, BMI = 31.8 ± 0.7) before and on the 4th (d4) and 28th (d28) days of a hypocaloric formula diet. Body composition was assessed with dual energy X-ray absorptiometry on dO and d28.

RESULTSL:— Mean daily energy intake during the diet was 1,100 ± 60 kcal (33% protein, 38% carbohydrate, and 29% fat). Mean weight loss was 6.2 ± 0.4 kg. Initial lipid profiles were similar in subjects with or without diabetes, and diabetes did not affect the responses. Dietary intervention resulted in early (d4) and late (d28) changes. Energy restriction(d4) reduced VLDL cholesterol and total triglyceride (TG) concentrations andincreased LDL particle size. With fat loss (d28), there were falls in total LDL cholesterol (free and esterified components), LDL TG, and LDL apolipoprotein B (apoB) concentrations. Reduction in central abdominal fat (but not other body fat) was correlated with a less atherogenic lipid profile: Δ abdominal fat versus Δ LDL free cholesterol, r = 0.65, P = 0.006 and versus Δ apoB, r = 0.64, P = 0.008.

CONCLUSIONS

Even in obese subjects with an average lipid profile, modest weight loss reduces atherogenicity, independently of type 2 diabetes, and abdominal fat loss is specifically related to such improvements.
Why Don't Women With Diabetes Plan Their Pregnancies?
Authors: Holing Emily V , Beyer Carla S , Brown Zane A , Connell Frederick A
Published: March 2007

OBJECTIVE

To determine why women with diabetes generally do not plan their pregnancies, consequently entering their pregnancies with poor blood glucose control and greatly increasing the risk of birth defects in their infants.

RESEARCH DESIGN AND METHODS

A population-based sample of 85 women with diabetes diagnosed before the index pregnancy were recruited within 6 months postpartum from 15 hospitals in the state of Washington. Women with planned and unplanned pregnancies were compared using qualitative and quantitative analysis of personal interviews, self-administered questionnaires, and medical record review.

RESULTS

Although most women (79%) knew they should optimize their blood glucose levels before conception, fewer than half (41%) of their pregnancies were planned. Women with planned pregnancies had significantly higher income and more education; were more likely to have private health insurance, to see an endocrinologist before pregnancy, to be happily married, and to be Caucasian; and were less likely to use tobacco. Most unplanned pregnancies were not contraceptive failures, but may have been consciously or subconsciously intended. Women with planned pregnancies generally described an ongoing and positive relationship with their health care providers. Women who felt that their doctors discouraged pregnancy were more likely to have an unplanned pregnancy than were women who had been reassured they could have a healthy baby.

CONCLUSIONS

Many women with diabetes still perceive negative messages about pregnancies and become pregnant without optimal planning. We believe there are many opportunities for increasing the proportion of women with diabetes who plan their pregnancies, particularly in the areas of prepregnancy information, support that women are given, and the quality of the relationships they experience within the health care system. It is crucial that couples be reassured that with pre-conception glucose control, almost all women with diabetes can have healthy babies.
Well-Being and Treatment Satisfaction in Older People With Diabetes
Authors: Petterson Tim , Lee Pauline , Hollis Sally , Young Bob , Newton Peggy , Dornan Tim
Published: March 2007

OBJECTIVE

To measure well-being and treatment satisfaction and their correlates in older people with diabetes.

RESEARCH DESIGN AND METHODS

A postal survey was conducted of 1,000 diabetic patients aged ≥ 60 years, representing 56% of the resident older diabetic population in an inner-city health district with a largely indigenous population of 230,000 people and a widely varied socioeconomic mix. Well-being and treatment satisfaction were measured with diabetes-specific instruments and correlated with patient data held in a central register.

RESULTS

There was an 81% response. The general well-being scores (median [interquartile range]) for patients on diet alone, tablets, and insulin were 54 (44–60), 53 (42–61), and 48 (35–56) (P < 0.001 comparing insulin with diet and tablets) compared with a scale maximum of 66. Treatment satisfaction scores were 35 (31–36), 35 (32–36), and 34 (30–36) (P < 0.001 comparing insulin with diet and tablets), scale maximum 36. Mean HbA1c concentrations were 5.0 ± 1.4% (for patients on diet alone), 5.8 ± 1.6% (tablets), and 6.6 ± 1.7% (insulin) (P < 0.001 for each difference). Neither well-being nor treatment satisfaction correlated with HbA1c. Insulin-treated patients were younger and had been diabetic longer than non-insulin-treated patients; their well-being remained slightly, but significantly, lower when adjusted for age, sex, BMI, and diabetes duration, but treatment satisfaction was no longer significantly different. Women had lower well-being than men.

CONCLUSIONS

It has proved possible to measure well-being and treatment satisfaction in a large community-based samples of older people with diabetes. At the level of glycemic control in this population, neither parameter correlated with HbA1c. The lower well-being in insulin-treated patients remained significant in multivariate analysis.
Association of Helicobacter pylori Infection With Cardiovascular and Cerebrovascular Disease in Diabetic Patients
Authors: de Luis Daniel A , Lahera Marcos , Cantón Rafael , Boixeda Daniel , San Román Antonio L , Aller Rocio , de La Calle Hermenegildo
Published: March 2007

OBJECTIVE

Infection by Helicobacter pylori has been epidemiologically linked to some extradigestive conditions, including ischemic heart disease. Diabetic patients are an at-risk population for cardiovascular and thrombo-occlusive cerebral disease. The aim of the study was to examine a possible relationship between H. pylori infection and cardiovascular or cerebrovascular disease in diabetic patients.

RESEARCH DESIGN AND METHODS

This was a cross-sectional case-control study with 127 diabetic patients (both IDDM and NIDDM). Special emphasis was placed on the detection of clinical macro- and microvascular complications, cardiovascular risk factors, acute phase reactants, and serological markers of increased cardiovascular disease risk. H. pylori infection was assessed through the determination of specific Ig-G titers, measured by a commercial enzyme-linked immunosorbent assay.

RESULTS

Coronary heart disease was more prevalent in diabetic patients with than without H. pylori (odds ratio [OR] 4.07; 95% Cl 1.21–13.6; P < 0.05). A history of thrombo-occlusive cerebral disease was also more frequent in H. pylori–positive diabetic patients (OR 4.8; 95% CI 1.24–18.51; P < 0.05). Other complications such as peripheral arteriopathy, advanced nephropathy, neuropathy, or retinopathy were no differently distributed according to serological status. Alterations in the levels of the following acute-phase reactants and blood chemistry determinations were significantly more profound in H. pylori–positive diabetic patients: high fibrinogen (P < 0.05), high erythrocyte sedimentation rate (P < 0.001), high triglycerides (P < 0.001), and low HDL cholesterol (P < 0.001). These values were also more deeply altered in H. pylori–positive diabetic patients with a history of coronary heart disease, thrombo-occlusive cerebral disease, or both, when compared with H. pylori–positive diabetic patients without those complications.

CONCLUSIONS

Our data indicate a possible association of H. pylori infection and the development of coronary heart disease, thrombo-occlusive cerebral disease, or both, in diabetic patients. The importance of this link is highlighted by the possibility of an effective intervention against H. pylori infection.
Successful Treatment With Plasmapheresis, Cyclophosphamide, and Cyclosporin A in Type B Syndrome of Insulin Resistance: Case report
Authors: Eriksson Jan W , Bremell Tomas , Eliasson Björn , Fowelin Jesper , Fredriksson Linda , Yu Zhi-Wen
Published: March 2007

CASE HISTORY

A woman born in 1949 was diagnosed in 1990 with systemic lupus erythematosus. She was treated with prednisolone, and < 1 year later she presented with marked hyperglycemia. Large doses of insulin were given four times per day. Even though the patient was thin (BMI 17.4 kg/m2), very little improvement was seen.

INVESTIGATIONS AND TREATMENT

Serum insulin levels were high, and a euglycemic clamp investigation confirmed severe insulin resistance. The patient's serum contained insulin receptor antibodies inhibiting insulin binding, and thus the patient had a type B syndrome of insulin resistance. After diet and exercise, glycemic control stabilized and insulin treatment was withdrawn. However, in late 1993 she was in a catabolic and hyperglycemic state even though prednisolone doses were increased and azathioprin was added. In early 1994 she was treated with plasmapheresis and cyclophosphamide i.v. Subsequently, cyclosporin A was started as a maintenance therapy in addition to azathioprin. There was a rapid and sustained clinical improvement. Since late 1994 and onward, there is no sign of diabetes or glucose intolerance and there are no demonstrable insulin receptor antibodies in the patient's serum.

DISCUSSION

Severe type B insulin resistance may respond favorably to treatment with plasmapheresis and cyclophosphamide followed by cyclosporin A in combination with azathioprin.
Growth Changes in Children and Adolescents With Short-Term Diabetes
Authors: Bognetti Emilio , Riva Maria Cristina , Bonfanti Riccardo , Meschi Franco , Viscardi Matteo , Chiumello Giuseppe
Published: March 2007

OBJECTIVE

Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents.

RESEARCH DESIGN AND METHODS

The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 ± 4.1 years) and control subjects (8.5 ± 4.2 years) at recruitment in the study was similar.

RESULTS

At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (−0.12 ± 2.1; −0.76 ± 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes.

CONCLUSIONS

Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.
Fasting Plasma Glucose Is a Useful Test for the Detection of Gestational Diabetes
Authors: Reichelt Angela J , Spichler Ethel R , Branchtein Leandro , Nucci Luciana B , Franco Laércio J , Schmidt Maria Inês ,   Brazilian Study of Gestational Diabetes (EBDG) Working Group
Published: March 2007

OBJECTIVE

To evaluate fasting plasma glucose as a screening test for states of gestational diabetes.

RESEARCH DESIGN AND METHODS

Baseline data of a cohort conducted in general prenatal care units in Brazil, enrolling 5,579 women aged ≥ 20 years with gestational ages of 24–28 weeks at the time of testing and no previous diagnosis of diabetes. A standardized 2-h 75-g oral glucose tolerance test was performed in 5,010 women. Gestational diabetes and its subcategories—diabetes and impaired glucose tolerance—were defined according to the 1994 World Health Organization panel recommendations. We evaluated screening properties of calculated sensitivity and specificity for fasting plasma glucose with receiver operator characteristic curves.

RESULTS

For detection of the subcategory diabetes, a fasting plasma glucose of 89 mg/dl jointly maximizes sensitivity (88%) and specificity (78%), identifying 22% of the women as test-positive. For detection of impaired glucose tolerance, a value of 85 mg/dl jointly maximizes sensitivity and specificity (68%), identifying as test-positive 35% of the women. Lowering the cut point to 81 mg/dl increases sensitivity to 81%, but decreases specificity to 54%, labeling as test-positive 49% of the women.

CONCLUSIONS

Fasting plasma glucose is a useful test for the screening of both subcategories of gestational diabetes, a threshold of 85 mg/dl being an acceptable option. Effective screening for the subcategory diabetes can be achieved using a cut point of 89 mg/dl. If greater emphasis is placed on the detection of impaired glucose tolerance, a lower value, 81 mg/dl, may be needed.
Ethnicity and Cardiovascular Disease: The incidence of myocardial infarction in white, South Asian, and Afro-Caribbean patients with type 2 diabetes (U.K. Prospective Diabetes Study 32)
Authors:   U.K. Prospective Diabetes Study Group
Published: March 2007

OBJECTIVE

To estimate the incidence of myocardial infarction (MI) by ethnicity in subjects with diabetes and to examine the effect of ethnicity, adjusting for differences in cardiovascular risk factors.

RESEARCH DESIGN AND METHODS

For a prospective study, 4,974 patients with newly diagnosed type 2 diabetes, aged 25–65 years, were recruited from 23 clinics around the U.K. between 1977 and 1991. Of these subjects, 82% were white, 10% were South Asians, and 8% were Afro-Caribbeans. Fatal and first nonfatal MIs were defined by criteria based on the World Health Organization's Multinational Study of Vascular Disease. Age-standardized incidence rates were calculated. Cox regression was used to assess the independent effect of ethnicity controlling for risk factors for MI measured at study entry.

RESULTS

Of the subjects, 295 had a fatal MI and 558 had a fatal or a first nonfatal MI. The age-standardized rate per 1,000 person years for fatal or nonfatal MI for whites was 14.6 (95% CI, 13.3–15.9), for Afro-Caribbeans 4.3 (2.5–7.0), and for South Asians 15.4 (10.6–21.4). The hazard ratio associated with Afro-Caribbean ethnicity for MI relative to whites was 0.3 (0.2–0.6) after adjusting for age, sex, year of study entry, systolic blood pressure, smoking, social class, total cholesterol, and HDL cholesterol, whereas the hazard ratio for South Asians was 1.2 (0.9–1.7).

CONCLUSIONS

This study found that after adjusting for conventional cardiovascular risk factors, U.K. Afro-Caribbean subjects with diabetes had a lower risk for MI than whites, whereas South Asians did not have a risk different from that of whites.
Role of Orlistat in the Treatment of Obese Patients With Type 2 Diabetes: A 1-year randomized double-blind study
Authors: Hollander Priscilla A , Elbein Steven C , Hirsch Irl B , Kelley David , McGill Janet , Taylor Terry , Weiss Stuart R , Crockett Samuel E , Kaplan Roy A , Comstock John , Lucas Charles P , Lodewick Peter A , Canovatchel William , Chung Jain , Hauptman Jonathan
Published: March 2007

OBJECTIVE

Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications.

RESEARCH DESIGN AND METHODS

In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28–40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured.

RESULTS

After 1 year of treatment, the orlistat group lost 6.2 ± 0.45% (mean ± SEM) of initial body weight vs. 4.3 ± 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost ≥ 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.

CONCLUSIONS

Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.
Distortion-Product Otoacoustic Emissions and Selective Sensorineural Loss in IDDM
Authors: Nardo Walter Di , Ghirlanda Giovanni , Paludetti Gaetano , Cercone Stefania , Saponara Caterina , Ninno Massimiliano Del , Girolamo Stefano Di , Magnani Paolo , Leo Mauro A S Di
Published: March 2007

OBJECTIVE

To provide information about possible subclinical damage of the cochlear outer hair cells (OHCs) by means of transiently evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in subjects with IDDM.

RESEARCH DESIGN AND METHODS

TEOAEs and DPOAEs were recorded in 47 IDDM patients with normal hearing and in age- and sex-matched nondiabetic subjects. Peripheral neuropathy was diagnosed by nerve conduction velocity (NCV) at the peroneal and surral nerves.

RESULTS

A subclinical peripheral neuropathy was found in 15 diabetic patients. Mean TEOAE amplitude was found to be significantly reduced in diabetic patients with a reduced NCV (7.6 ± 3.2 dB; Scheffé's test: P = 0.03), but not in those without neuropathy (9.5 ± 4.3 dB), with respect to control subjects (11 ± 3.1 dB). Neuropathic patients also showed mean reduced DPOAE amplitude values in the region of middle and high frequencies from 1,306 to 5,200 Hz (P < 0.05), whereas no difference was found at the lowest-frequency amplitudes. A frequency-selective reduction of DPOAEs was also found in non-neuropathic patients (P < 0.05) in the region of higher frequencies at 3,284, 4,126, and 5,200 Hz compared with control subjects. No correlations were found among duration of diabetes, HbA1c values, TEOAEs and DPOAEs.

CONCLUSIONS

Our results suggest that IDDM patients show an early abnormality of the micromechanical properties of the OHCs. In IDDM patients without a subclinical peripheral neuropathy, damage is limited to the higher frequencies and can be detected only by DPOAEs, whereas in IDDM patients with neuropathy, damage also involves the middle range of frequencies and can be detected by TEOAEs and DPOAEs. Therefore, DPOAEs seem to be able to detect the earliest cochlear selective-frequency dysfunction in IDDM patients without peripheral neuropathy. DPOAEs appear to be of greater clinical interest than TEOAEs; the former seem to be frequency specific and can be recorded at any chosen frequency, including high frequencies.
Long-Term Lisinopril Therapy Reduces Exercise-Induced Albuminuria in Normoalbuminuric Normotensive IDDM Patients
Authors: Tuominen Juha A , Ebeling Pertti , Koivisto Veikko A
Published: March 2007

OBJECTIVE

To study the effect of lisinopril on the exercise-induced urinary albumin excretion rate.

RESEARCH DESIGN AND METHODS

A total of 26 IDDM patients with normoalbuminuria were randomized into two groups, with one group receiving placebo (n = 13, age 36 ± 3 years, BMI 24.5 ± 1.1 kg/m2) and the other group receiving an average of 15 mg lisinopril daily (n = 13, age 34 ± 2 years, BMI 24.4 ± 0.9 kg/m2). Overnight and exercise-induced urinary albumin excretion rate was measured at baseline and after 1 and 2 years of treatment. Two patients in the placebo group and none in the lisinopril group developed microalbuminuria.

RESULTS

In the lisinopril group, the exercise-induced urinary albumin excretion rate diminished 46% after the 1st year (P = 0.059) and 66% (P < 0.01) after the 2nd year. However, it remained unchanged in the control group. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were similar at baseline and after 1 year, but at 2 years, sBP was 13 mmHg lower (P = 0.03) and dBP was 9 mmHg lower (P = 0.052) in the lisinopril group as compared with the control group. The dBP decreased significantly at 1 and 2 years in the lisinopril group, while there was no significant change in the sBP. In the whole group at baseline, the overnight albumin excretion rate correlated with HbA1c (r = 0.50, P < 0.01) and the duration of diabetes (r = 0.39, P < 0.05), and sBP correlated with both the overnight (r = 0.42, P < 0.05) and the exercise-induced (r = 0.48, P < 0.05) albumin excretion rate.

CONCLUSIONS

Glycemic control and blood pressure are directly related to the overnight albumin excretion rate also in normotensive normoalbuminuric IDDM patients. Lisinopril treatment reduces the exercise-induced urinary albumin excretion rate in such patients. These data suggest a protective effect of lisinopril against the development of microalbuminuria.
Effects of Changing Diagnostic Criteria on the Risk of Developing Diabetes
Authors: Dinneen Sean F , Maldonado David , Leibson Cynthia L , Klee George G , Li Hongzhe , Melton L Joseph , Rizza Robert A
Published: March 2007

OBJECTIVE

The American Diabetes Association (ADA) has recommended that the fasting plasma glucose (FPG) level used to diagnose diabetes be changed from 7.8 mmol/l (the level recommended by the National Diabetes Data Group [NDDG] in 1979) to 7.0 mmol/l. We examined the impact of this change on rates of progression to overt diabetes from different levels of FPG.

RESEARCH DESIGN AND METHODS

Using the laboratory database of Mayo Clinic, we assembled a cohort of 8,098 nondiabetic Olmsted County residents 40 years of age or older on 1 July 1983. Subjects were followed for a median of 9 years.

RESULTS

Among 7,567 individuals with follow-up FPG data, 778 (10.3%) progressed to ADA diabetes and 513 (6.8%; P < 0.0001) progressed to NDDG diabetes. The risk of developing ADA diabetes was 7, 19, and 39% for individuals with initial FPG values in the ranges of <5.6, 5.6–6.0, and 6.1–6.9 mmol/l, respectively. For progression to NDDG diabetes, the respective risks were 3, 11, and 25%. A clear gradient of risk was observed within the “normal” range of FPG (<5.6 mmol/l). Among the 793 individuals who developed ADA diabetes, 222 (29%) developed NDDG diabetes simultaneously and 291 (37%) developed NDDG diabetes later. In all FPG subgroups, progression to ADA diabetes occurred ∼7 years sooner than progression to NDDG diabetes.

CONCLUSIONS

The baseline level of FPG is a major predictor of an individual's risk of developing diabetes. The proposed change in the diagnostic criteria for diabetes will lead to earlier diagnosis among individuals who are destined to develop the disease.
Two-Step Islet Autoantibody Screening for Risk Assessment of Type 1 Diabetes in Relatives
Authors: Pastore Matteo R , Bazzigaluppi Elena , Bonfanti Riccardo , Dozio Nicoletta , Sergi Alessandro , Balini Annalisa , Belloni Cristina , Meschi Franco , Bonifacio Ezio , Bosi Emanuele
Published: March 2007

OBJECTIVE

To examine the performance of islet cell antibodies (ICAs) and antibodies to glutamate decarboxylase (GADA), IA-2 (IA-2 antibody [IA-2A]), and insulin (insulin autoantibody [IAA]), alone and in combination, in assessing type 1 diabetes risk within type 1 diabetic families to identify a practical and effective screening strategy for predicting type 1 diabetes in relatives.

RESEARCH DESIGN AND METHODS

ICA, GADA, IA-2A, and IAA were determined in 806 first-degree relatives participating in a prospective type 1 diabetes family study (median follow-up 6.17 years, range 0.6–8.3). The conferred risk of developing type 1 diabetes within 6 years was evaluated by Kaplan-Meier for each antibody marker, used alone or in combination.

RESULTS

ICAs were detected in 3%, GADA in 5.1%, IA-2A in 2.5%, and IAA in 3.7% of relatives; ≥1 antibody markers were detected in 10.7% of relatives and ≥2 were detected in 1.9% of relatives. The risk of type 1 diabetes at 6 years was 1.5% in relatives with only 1 marker and 24.8% in relatives with ≥2 markers. As a practical and effective strategy for type 1 diabetes risk assessment in relatives, this study indicates a first-step screening based on GADA and IA-2A measurement—which identified 6.5% of relatives, including all who developed the disease, with a 6-year type 1 diabetes risk of 9.0%—followed by a second step based on ICA and IAA measurement in relatives with either GADA or IA-2A, which identified a total of 1.9% of all relatives as having ≥2 markers, and a 6-year risk of 24.8%, including 6 of 7 who developed type 1 diabetes.

CONCLUSIONS

A two-step antibody screening, based first on GADA and IA-2A and then on ICA and IAA measurements in identified individuals, is likely to be a practical, sensitive, and effective strategy for predicting type 1 diabetes in first-degree relatives.
Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.
Authors: Reiber G E , Vileikyte L , Boyko E J , del Aguila M , Smith D G , Lavery L A , Boulton A J
Published: March 2007

OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.
Peripheral atherosclerosis and serum lipoprotein(a) in diabetes.
Authors: Wollesen F , Dahlén G , Berglund L , Berne C
Published: March 2007

OBJECTIVE: Serum lipoprotein(a) [Lp(a)] is strongly associated with atherosclerosis in nondiabetic individuals. To see if atherosclerosis is also associated with serum Lp(a) in both IDDM and NIDDM, we determined the correlation between the toe systolic blood pressure index (TSPI) and serum Lp(a) in tightly controlled diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS: Cross-sectional study of 57 IDDM and 35 NIDDM patients. All patients had been under strict glycemic control for at least 6 months. The main outcome measure was TSPI of both lower extremities. In addition, we measured serum Lp(a) and other serum lipids, serum uric acid, total plasma homocysteine, plasma C-peptide, HbA1c, albumin excretion rate, glomerular filtration rate, BMI, abdominal fat distribution, left ventricular hypertrophy, probabilities for cardiovascular disease (CVD), and routine clinical parameters. RESULTS: TSPI was closely and independently related to serum Lp(a) in IDDM patients: R2 = 0.2999, partial P = 0.0005, and in NIDDM patients: R2 = 0.7326, partial P = 0.0030. TSPI was associated with symptoms of CVD. Median serum Lp(a) concentration was normal in IDDM (45 mg/l [range 10-870]) and NIDDM (72 mg/l [11-803]) patients. CONCLUSIONS: Systemic atherosclerosis measured as the degree of peripheral occlusive arterial disease is strongly associated with serum Lp(a) in both IDDM and NIDDM patients. Serum Lp(a), however, is normal in both types of diabetic patients. Thus, it is indicated that serum Lp(a) should be measured in diabetic patients when assessing their risk profile for atherosclerosis.
High normal blood pressure, hypertension, and the risk of type 2 diabetes in Japanese men. The Osaka Health Survey.
Authors: Hayashi T , Tsumura K , Suematsu C , Endo G , Fujii S , Okada K
Published: March 2007

OBJECTIVE: To investigate the relationship between high normal blood pressure or hypertension and the risk of developing type 2 diabetes in a large Japanese cohort. RESEARCH DESIGN AND METHODS: We enrolled 7,594 Japanese men aged 35-60 years who did not have diabetes or impaired fasting glucose at study entry. Type 2 diabetes was defined as a fasting plasma glucose level of > or = 126 mg/dl or a 2-h postload plasma glucose level of > or = 200 mg/dl. High normal blood pressure was defined as no history of hypertension and a systolic blood pressure of > or = 130 and < 140 mmHg or a diastolic blood pressure of > or = 85 and < 90 mmHg. Subjects were considered to have hypertension if they had a systolic blood pressure > or = 140 mmHg, if they had a diastolic blood pressure > or = 90 mmHg, or if they were taking anti-hypertensive medications. RESULTS: We confirmed 600 cases of type 2 diabetes during the 72,946 person-years of follow-up. Both high normal blood pressure and hypertension were associated with the risk of type 2 diabetes. Compared with normotensive men, men with high normal blood pressure had a multiple adjusted relative risk (RR) of 1.39 (95% CI 1.14-1.69), and men with hypertension had a multiple adjusted RR of 1.76 (1.43-2.16). Even among lean men (BMI < 22.7 kg/m2), men with high normal blood pressure had a multiple adjusted RR of 1.71 (1.20-2.42), and men with hypertension had a multiple adjusted RR of 2.02 (1.34-3.05) compared with normotensive men. CONCLUSIONS: High normal blood pressure and hypertension are associated with an increased risk of developing type 2 diabetes.
LDL particle size in relation to insulin, proinsulin, and insulin sensitivity. The Insulin Resistance Atherosclerosis Study.
Authors: Festa A , D'Agostino R , Mykkänen L , Tracy R P , Hales C N , Howard B V , Haffner S M
Published: March 2007

OBJECTIVE: LDL particles are heterogeneous in terms of size and density; small dense LDL particles are considered more atherogenic than larger LDL particles. The aim of this study was to investigate the interrelationships among LDL size, insulin, proinsulin (intact and split), and insulin sensitivity in a tri-ethnic population with varying degrees of glucose tolerance (n = 1,549) in the Insulin Resistance Atherosclerosis Study. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test with minimal model analysis. Proinsulin levels were measured using highly sensitive assays without detectable cross-reactivity with insulin, and LDL size was determined by gradient-gel electrophoresis. RESULTS: In univariate analyses, LDL size was related to various features of the insulin resistance syndrome, including fasting insulin (r = -0.18), intact proinsulin (r = -0.24), split proinsulin (r = -0.24), the proinsulin-to-insulin ratio (r = -0.14), and insulin sensitivity (r = 0.21; all P < 0.0001). In a multivariate regression model (adjusted for age, BMI, ethnicity, and clinic), triglyceride levels (P = 0.0001), HDL cholesterol (P = 0.0001), sex (P = 0.002), and proinsulin (P = 0.01) were significantly related to LDL size. In the same model stratified by sex, LDL size was significantly inversely related to proinsulin in men (P = 0.005 and P = 0.04 after further adjustment for the glucose tolerance status), but not in women (P > 0.15). CONCLUSIONS: We found an inverse relation of proinsulin to LDL particle size in a large tri-ethnic population with varying degrees of glucose tolerance. This relation was independent of age, BMI, and triglyceride and HDL cholesterol concentrations, and was more pronounced in men than in women.
Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study.
Authors: Allen H F , Klingensmith G J , Jensen P , Simoes E , Hayward A , Chase H P
Published: March 2007

OBJECTIVE: We undertook this study to test whether Bacillus Calmette-Guerin (BCG) vaccine preserves beta-cell function and increases the remission rate in children with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized double-blind placebo-controlled trial offered to children referred to the Barbara Davis Center for Childhood Diabetes or the Baystate Medical Center with a diagnosis of new-onset type 1 diabetes. There were 94 children aged 5-18 years who received either BCG or saline intradermally within 4 months of onset of symptoms and who were then evaluated at 3-month intervals for 2 years. The primary end point was remission, defined as insulin independence for 4 weeks. Secondary end points were C-peptide levels (fasting and in response to a mixed meal challenge), insulin dose, and HbA1c. RESULTS: Of the patients, 47 were randomized to each arm; 7 in the placebo group and 9 in the BCG group did not complete 1 year of the study and are not included in the analysis. One patient from each group achieved remission. Fasting and stimulated C-peptide levels did not differ by treatment arm but declined in both groups and were lower initially and during the entire 2-year period in younger children. Insulin requirements and HbA1c levels did not differ in the two groups. CONCLUSIONS: Vaccination with BCG at the time of onset of type 1 diabetes does not increase the remission rate or preserve beta-cell function.