bluuebunny/crossref_metadata_2025 huggingface dataset:
High Incidence of Childhood Type 1 Diabetes in Liguria, Italy, From 1989 to 1998
Authors: Cotellessa Mario , Barbieri Paola , Mazzella Massimo , Bonassi Stefano , Minicucci Laura , Lorini Renata
Published: March 2007

OBJECTIVE—Assessing updated incidence of type 1 diabetes in 0- to 14-year-old children in Liguria, a Northwest region of Italy.

RESEARCH DESIGN AND METHODS—Incident cases were recorded prospectively from 1989 to 1998. Incidence rates (IRs) were standardized to the 1999 world population using the direct method. The independent effect of sex, age, residence, and calendar year was estimated with Poisson regression model. The degree of ascertainment was calculated in accordance to capture/recapture method.

RESULTS—During 10 full calendar years, 219 new cases of type 1 diabetes in children were diagnosed in Liguria. The standardized IR over the 10-year period was 12.56 cases per 100,000 per year (95% CI 11.0–14.3). The sex-specific IR among men and women was 14.15 and 10.88, respectively. The age-specific IR was higher in the 10- to 14-year-old age-group (15.01/100,000) than in 0- to 4-year-old age-group (9.01/100,000) and in the 5- to 9-year-old age-group (13.03/100,000).

CONCLUSIONS—The IR of type 1 diabetes in Liguria is among the highest in Southern Europe and approaches IRs 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 type 1 diabetes does not seem to reflect the simple North-South gradient reported in several previous works.
Treating Hypertension in Diabetic Nephropathy
Authors: Tomlinson Jeremy W. , Owen Katharine R. , Close Colin F.
Published: March 2007

OBJECTIVE—Control of hypertension in patients with diabetic nephropathy improves mortality and slows progression to end-stage renal disease. However, blood pressure is difficult to treat; multiple drug combination therapy is required and treatment algorithms to establish this are lacking. We used a stepped-care algorithm, centered on maximum doses of an ACE inhibitor or angiotensin II receptor blocker, to treat hypertension according to American Diabetes Association recommended blood pressure target goals (<130/80 mmHg) in patients with diabetic nephropathy.

RESEARCH DESIGN AND METHODS—We treated 49 consecutive patients with diabetes (13 with type 1 and 36 with type 2), diabetic nephropathy, and proteinuria ≥500 mg/24 h with a stepped-care blood pressure treatment algorithm. The level of blood pressure control achieved at most recent follow-up was assessed.

RESULTS—Patients were followed for a median of 18 months (range 9–48). Mean blood pressure achieved was 140/75 ± 23/14 mmHg in patients with type 1 diabetes and 146/76 ± 22/14 mmHg in patients with type 2 diabetes. Target blood pressure was reached in 16 (33%) patients, 6 of 13 patients with type 1 diabetes and 10 of 36 patients with type 2 diabetes, whereas systolic blood pressure remained above the target level in the remaining patients. There was no difference in baseline blood pressure, proteinuria, or serum creatinine level between patients who were treated to target and those who were not.

CONCLUSIONS—Levels of blood pressure control similar to those achieved in clinical trials in diabetic nephropathy were obtained with a stepped-care algorithm. However, in most patients, systolic blood pressure was difficult to control to target despite the use of multiple drug combination therapy.
Steroids in Adult Men With Type 1 Diabetes
Authors: van Dam Eveline W.C.M. , Dekker Jacqueline M. , Lentjes Eef G.W.M. , Romijn Fred P.T.H.M. , Smulders Yvo M. , Post Wendy J. , Romijn Johannes A. , Krans H. Michiel J.
Published: March 2007

OBJECTIVE—To compare steroids and their associations in men with type 1 diabetes and healthy control subjects.

RESEARCH DESIGN AND METHODS—We studied 52 adult men with type 1 diabetes without microvascular complications, compared with 53 control subjects matched for age and BMI. Steroids and their binding globulins were assessed in a single venous blood sample and a 24-h urine sample.

RESULTS—In adult men with type 1 diabetes, total testosterone did not differ from healthy control subjects, but sex hormone–binding globulin (SHBG) (42 [14–83] vs. 26 [9–117] nmol/l, P < 0.001), cortisol-binding globulin (CBG; 0.87 ± 0.17 vs. 0.73 ± 0.10 nmol/l, P < 0.001), and cortisol levels (0.46 ± 0.16 vs. 0.39 ± 0.14 nmol/l, P < 0.01) were higher. The free testosterone index was lower (60 [17–139] vs. 82 [24–200], P < 0.001), and the calculated free testosterone was slightly lower (497 [115] vs. 542 [130], P < 0.064), but the pituitary-gonadal axis was not obviously affected in type 1 diabetes. The calculated free serum cortisol was not different, and 24-h urinary free cortisol excretion was lower in type 1 diabetes (121 [42–365] vs. 161 [55–284] nmol/24 h, P < 0.009). Testosterone was mainly associated with SHBG. Estimated portal insulin was a contributer to SHBG in control subjects but not in type 1 diabetes. Cortisol was associated with CBG. HbA1c contributed to CBG in men with diabetes but not in control subjects, whereas estimated portal insulin did not contribute.

CONCLUSIONS—Adult men with fairly controlled type 1 diabetes without complications who are treated with subcutaneous insulin have a tendency to hypogonadism, as reflected by lower free testosterone levels in the presence of similar total testosterone levels and higher SHBG levels.
A Cross-Sectional Study of Alcohol Consumption Patterns and Biologic Markers of Glycemic Control Among 459 Women
Authors: Kroenke Candyce H. , Chu Nain-Feng , Rifai Nader , Spiegelman Donna , Hankinson Susan E. , Manson JoAnn E. , Rimm Eric B.
Published: March 2007

OBJECTIVE—Little research has explored associations of drinking patterns with glycemic control, especially among women. Our objective was to determine the relationship of patterns of alcohol consumption—including average daily consumption, weekly frequency of consumption, drinking with meals, and beverage type—with biologic markers of insulin resistance in young women.

RESEARCH DESIGN AND METHODS—This study was cross-sectional in design. The subjects consisted of a stratified random subpopulation of 459 U.S. normal-weight and overweight female nurses, 33–50 years of age, drawn from the Nurses’ Health Study II and sampled for distinct drinking patterns. Women provided blood samples and detailed information on dietary and lifestyle factors between 1995 and 1999. The main outcome measures were fasting insulin, C-peptide, and HbA1c.

RESULTS—Adjusting for age, smoking, physical activity, television watching, BMI, and several dietary factors, average alcohol intake was inversely associated with HbA1c (units in percentage of HbA1c): 0 g/day (reference = 5.36%), 0.1 to <5.0 g/day (−0.04%), 5.0 to <15.0 g/day (−0.09%), 15.0 to <25.0 g/day (−0.10%), and ≥25.0 g/day (−0.17%) (P value, test for trend <0.001). We found an inverse association of alcohol intake and insulin, but only for women with a BMI ≥25 kg/m2. Specifically, insulin levels were lowest for episodic drinkers consuming ≥2 drinks per day on 0–3 days per week. Consumption with meals and type of alcoholic beverage did not further influence these results.

CONCLUSIONS—Moderate alcohol consumption of 1–2 drinks per day on a few to several days of the week may have a beneficial glycemic effect, particularly among overweight women.
Association Between Insulin Sensitivity and Post-Glucose Challenge Plasma Insulin Values in Overweight Latino Youth
Authors: Weigensberg Marc J. , Cruz Martha L. , Goran Michael I.
Published: March 2007

OBJECTIVE—To determine associations between directly measured insulin sensitivity (SI) and oral glucose tolerance test (OGTT)-derived plasma insulin values, or calculated SI indices, in overweight peripubertal Latino children at risk for type 2 diabetes.

RESEARCH DESIGN AND METHODS—Thirty overweight Latino children with a family history of type 2 diabetes, aged 8–13 years, Tanner stages 1–2, underwent an OGTT. Fasting and 2-h plasma insulin values and OGTT-derived SI indices were compared with SI derived from a frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis, before and after adjustment for total body fat and lean tissue mass, or BMI.

RESULTS—FSIGTT-derived SI for all subjects was 1.62 ± 0.78 × 10−4 min −1 · (μU/ml), with no sex differences. SI correlated (all P values < 0.001) with fasting (r = −0.57) and 2-h (r = −0.58) plasma insulin and all SI indices (r = −0.57 to 0.67). After adjusting for total body fat and lean tissue mass, or BMI, the associations between SI and either fasting insulin or fasting SI indices were no longer significant. However, the 2-h insulin and post-glucose challenge SI indices maintained significant independent associations with SI, even after adjustment for body composition.

CONCLUSIONS—In overweight, peripubertal Latino children at risk for type 2 diabetes, the 2-h plasma insulin value and postchallenge SI indices are better independent correlates of SI than fasting values, after accounting for body composition. The 2-h insulin may therefore be superior to fasting insulin as a single blood sample value for clinical or epidemiological estimates of SI, especially when combined with assessment of body composition.
Use of Antibiotics Is Not Associated With Decreased Risk of Myocardial Infarction Among Patients With Diabetes
Authors: Karter Andrew John , Thom David H. , Liu Jennifer , Moffet Howard H. , Ferrara Assiamira , Selby Joe V.
Published: March 2007

OBJECTIVE—To study the relationship between exposure to antibiotic treatment and risk of subsequent myocardial infarction (MI) in patients with diabetes.

RESEARCH DESIGN AND METHODS—A case-control design was used to assess the effect of previous antibiotic exposure in diabetes patients with acute, nonfatal or fatal MI (case subjects) and individually matched control subjects (four control subjects to one case subject, matched on sex, age, and index date). Subjects were sampled from the Northern California Kaiser Permanente Diabetes Registry, a well-characterized, ethnically diverse diabetic population from Kaiser Permanente Medical Care Program, Northern California Region. MI events were ascertained during a 2-year observation period (1998–1999). Separate conditional logistic regression models were specified to assess antibiotic exposure history (cephalosporins only, penicillins only, macrolides only, quinolones only, sulfonamides only, tetracyclines only, as well as more than one, any, or no antibiotic) for three nested windows before the index date (0–6 months, 0–12 months, 0–24 months), facilitating assessment of whether the potential effect was dependent on the timing of the exposure.

RESULTS—A total of 1,401 MI case subjects were observed. Odds ratios were calculated in models adjusted for age, sex, race, education attainment, time since diabetes diagnosis, diabetes type and treatment, use of diet and exercise, total cholesterol, HDL cholesterol, triglyceride levels, hypertension, elevated urinary albumin excretion, serum creatinine, BMI, and smoking. We found no evidence of a protective effect of any of these therapeutic classes of antibiotics during any of the three time frames.

CONCLUSIONS—Our study does not support the hypothesis that use of antibiotics has a protective effect for prevention of coronary heart disease in diabetic patients.
The Aging of Elastic and Muscular Arteries
Authors: Cameron James D. , Bulpitt Christopher J. , Pinto Elisabete S. , Rajkumar Chakravarthi
Published: March 2007

OBJECTIVE—To compare age-related changes in the mechanical properties of different arterial segments in normal volunteers and subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—In 169 subjects (diabetic n = 57 and nondiabetic n = 112), we assessed the mechanical properties of three arterial segments of differing wall composition. Pulse wave velocity (PWV) was measured noninvasively in a thoraco-abdominal segment (carotid femoral PWV [PWVcf]), in an upper limb muscular artery (carotid radial PWV [PWVcr]), and from the aorta to the finger (PWV from the aorta to the finger [PWVfin]). Central aortic compliance (CAC) was also measured.

RESULTS—Average CAC was lower (0.662 vs. 0.850, P < 0.05) and all measures of PWV tended to be faster in diabetic subjects despite the fact that they were, on average, 10 years younger. However, these measures were not related to age in diabetic subjects. After correcting for blood pressure, only PWVcf was associated with age in nondiabetic subjects (P < 0.001). Expressing results as ratios of nonelastic to elastic arterial segments (i.e., PWVcr-to-PWVcf and PWVfin-to-PWVcf) improved the relationship with age. Both PWVcr-to-PWVcf and PWVfin-to-PWVcf were significantly associated with age in nondiabetic subjects (r = −0.59, P < 0.001; r = −0.57, P < 0.001) but not in diabetic subjects (r = −0.15, P = 0.302; r = −0.24, P = 0.129). Multivariate analysis showed that the ratios were not associated with systolic blood pressure.

CONCLUSIONS—There are significant differences in the rate of age-related decline in vascular stiffness in elastic arteries of nondiabetic compared with diabetic arteries. Diabetic arteries appear to age at an accelerated rate at an earlier age and then reach a functional plateau.
Elevated Blood Interleukin-6 Levels in Hyperketonemic Type 1 Diabetic Patients and Secretion by Acetoacetate-Treated Cultured U937 Monocytes
Authors: Jain Sushil K. , Kannan Krishnaswamy , Lim Gideon , Matthews-Greer Janice , McVie Robert , Bocchini Joseph A.
Published: March 2007

OBJECTIVE—Diabetic patients have elevated blood levels of interleukin-6 (IL-6), which is known to increase inflammation and the development of vascular disease and atherosclerosis. This study examined the hypothesis that ketosis increases the circulating levels of IL-6 in type 1 diabetic patients as well as the secretion of IL-6 in vitro in a cell culture model using U937 monocytes.

RESEARCH DESIGN AND METHODS—Fasting blood was obtained from type 1 diabetic patients and healthy siblings. To examine the effect of ketosis, U937 monocytes were cultured with ketone bodies (acetoacetate [AA], β-hydroxybutyrate [BHB]) in the presence or absence of high glucose levels in the medium at 37°C for 24 h. IL-6 was determined by the sandwich enzyme-linked immunosorbent assay method, and intracellular reactive oxygen species (ROS) generation was detected using dihydroethidium dye.

RESULTS—The blood level of IL-6 was higher in hyperketonemic (HK) diabetic patients than in normoketonemic (NK) diabetic patients (P < 0.05) and normal control subjects (P < 0.05). There was a significant correlation between ketosis and IL-6 levels (r = 0.36, P < 0.04, n = 34) in the blood of diabetic patients. Cell culture studies found that exogenous addition of the ketone body AA, but not BHB, increases IL-6 secretion and ROS generation in U937 cells. N-acetylcysteine (NAC) prevented the IL-6 secretion in acetoacetate-treated U937 monocytes.

CONCLUSIONS—This study demonstrates that hyperketonemia increases IL-6 levels in the blood of type 1 diabetic patients and that NAC can inhibit IL-6 secretion by U937 monocytic cells cultured in a ketotic medium.
Cardiorespiratory Fitness and Vigorous Leisure-Time Physical Activity Modify the Association of Small Size at Birth With the Metabolic Syndrome
Authors: Laaksonen David E. , Lakka Hanna-Maaria , Lynch John , Lakka Timo A. , Niskanen Leo , Rauramaa Rainer , Salonen Jukka T. , Kauhanen Jussi
Published: March 2007

OBJECTIVE—Small size at birth has been associated with components of the metabolic syndrome, but little is known about the association with the metabolic syndrome itself or whether leisure-time physical activity (LTPA) and cardiorespiratory fitness modify that association. We studied the association of size at birth with the metabolic syndrome.

RESEARCH DESIGN AND METHODS—Birth weight and length, the metabolic syndrome (World Health Organization criteria), LTPA over the previous 12 months, and Vo2max were assessed in 462 nondiabetic middle-aged Finnish men who were part of a population-based cohort study.

RESULTS—Men with a ponderal index (kg/m3) at birth in the lower third had higher fasting insulin and glucose levels than men in the upper third in age-adjusted analyses and were at least twofold more likely to have the metabolic syndrome, even in men without cardiovascular disease. Adjustment for childhood or adult socioeconomic status or adult BMI did not attenuate the association. Thinness at birth was even more clearly associated with hyperinsulinemia and the metabolic syndrome in men engaging in <25 min/wk of vigorous LTPA and in men with a Vo2max <28.6 ml · kg−1 · min−1 or <2.44 l/min. In active and fit men, however, the association was absent.

CONCLUSIONS—Small size at birth was associated with the metabolic syndrome in middle-aged men already before development of diabetes or cardiovascular disease. Thinness at birth may carry with it lifelong metabolic consequences, but regular strenuous physical activity and maintenance of cardiorespiratory fitness may alleviate or eliminate those consequences.
Specialist Nurse-Led Intervention to Treat and Control Hypertension and Hyperlipidemia in Diabetes (SPLINT)
Authors: New John P. , Mason James M. , Freemantle Nick , Teasdale Sue , Wong Louise M. , Bruce Nick J. , Burns John A. , Gibson John M.
Published: March 2007

OBJECTIVE—To determine the effectiveness of specialist nurse-led clinics for hypertension and hyperlipidemia provided for diabetic patients receiving hospital-based care.

RESEARCH DESIGN AND METHODS—This study was a randomized controlled implementation trial at Hope Hospital, Salford, U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure (≥140/80 mmHg), raised total cholesterol (≥5.0 mmol/l), or both. Individuals with diabetes were randomized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics. Nurses provided clinics for participants, with attendance every 4–6 weeks, until targets were achieved. Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines. Patients with both conditions were eligible for enrollment in either or both clinics. At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register. Data relating to deaths were obtained from the national strategic tracing service. The primary outcome was the odds ratio of achieving targets in hypertension and hyperlipidemia, attributable to the specialist nurse-led intervention.

RESULTS—Overall, specialist nurse-led clinics were associated with a significant improvement in patients achieving the target after 1 year (odds ratio [OR] 1.37 [95% CI 1.11–1.69], P = 0.003). This primary analysis revealed a borderline difference in effect between the two types of clinics (test for interaction between groups: P = 0.06). Secondary analysis, consistent with the prior beliefs of the health care professionals involved, suggested that targets were achieved more frequently in patients enrolled in the specialist nurse-led clinic for hyperlipidemia (OR 1.69 [1.25–2.29], P = 0.0007) than for hypertension (OR 1.14 [0.86–1.51], P = 0.37). Intervention (enrolled to either or both clinics) was associated with a reduction in all-cause mortality (OR 0.55 [0.32–0.92], P = 0.02).

CONCLUSIONS—This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of patients with diabetes. If the standards of care recommended in the National Service Framework for Diabetes are to be achieved, then such proven methods for delivering care must be adopted.
Management of Uncontrolled Hypertension in a Nurse-Led Clinic Compared With Conventional Care for Patients with Type 2 Diabetes
Authors: Denver Elizabeth A. , Barnard Maria , Woolfson Robin G. , Earle Kenneth A.
Published: March 2007

OBJECTIVE—To compare the effectiveness of a nurse-led hypertension clinic with conventional community care in general practice in the management of uncontrolled hypertension in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We studied 120 men and women outpatient attendees (61% non-Caucasian) with type 2 diabetes and a seated blood pressure (BP) ≥140/80 mmHg. All patients were being treated for hypertension, and 71% had increased urinary albumin excretion (UAE). Patients were allocated to either a nurse-led hypertension clinic or conventional primary care. The primary outcome measure was a change in systolic BP. Secondary outcome measures were total cholesterol, HDL cholesterol, total triglycerides, HbA1c, UAE, serum creatinine, and changes in absolute stroke and coronary heart disease (CHD) risk scores.

RESULTS—The mean (95% CI) difference in the decrement of systolic BP was 12.6 mmHg (5.9–19.3) (P = 0.000) in favor of the nurse-led group, whose patients were three times more likely to a reach target systolic BP <140 mmHg compared with conventional care (P = 0.003). A significant fall in 10-year CHD (P = 0.004) and stroke risk (P = 0.000) scores occurred only in the nurse-led group. There were no significant differences in the reduction of diastolic BP or any of the other secondary outcome measures at 6 months.

CONCLUSIONS—Compared with conventional care, a nurse-led hypertension clinic is a more effective intervention for patients with type 2 diabetes and uncontrolled hypertension. A target systolic BP <140 mmHg is more readily achieved and may be associated with significant reductions in 10-year cardiovascular disease risk scores.
Impact of Population Management With Direct Physician Feedback on Care of Patients With Type 2 Diabetes
Authors: Grant Richard W. , Hamrick Hope E. , Sullivan Christine M. , Dubey Anil K. , Chueh Henry C. , Cagliero Enrico , Meigs James B.
Published: March 2007

OBJECTIVE—Population-level strategies may improve primary care for diabetes. We designed a controlled study to assess the impact of population management versus usual care on metabolic risk factor testing and management in patients with type 2 diabetes. We also identified potential patient-related barriers to effective diabetes management.

RESEARCH DESIGN AND METHODS—We used novel clinical software to rank 910 patients in a diabetes registry at a single primary care clinic and thereby identify the 149 patients with the highest HbA1c and cholesterol levels. After review of the medical records of these 149 patients, evidence-based guideline recommendations regarding metabolic testing and management were sent via e-mail to each intervention patient’s primary care provider (PCP). Over a 3-month follow-up period, we assessed changes in the evidence-based management of intervention patients compared with a matched cohort of control patients receiving usual care at a second primary care clinic affiliated with the same academic medical center.

RESULTS—In the intervention cohort, PCPs followed testing recommendations more often (78%) than therapeutic change recommendations (36%, P = 0.001). Compared with the usual care control cohort, population management resulted in a greater overall proportion of evidence-based guideline practices being followed (59 vs. 45%, P = 0.02). Most intervention patients (62%) had potential barriers to effective care, including depression (35%), substance abuse (26%), and prior nonadherence to care plans (18%).

CONCLUSIONS—Population management with clinical recommendations sent to PCPs had a modest but statistically significant impact on the evidence-based management of diabetes compared with usual care. Depression and substance abuse are prevalent patient-level adherence barriers in patients with poor metabolic control.
Predicted Costs and Outcomes From Reduced Vibration Detection in People With Diabetes in the U.S.
Authors: Shearer Arran , Scuffham Paul , Gordois Adam , Oglesby Alan
Published: March 2007

OBJECTIVE—The ability to perceive vibration (vibration detection) has been shown to be a good predictor of the long-term complications of diabetic peripheral neuropathy (DPN). We aimed to estimate the predicted complications and costs for the U.S. health care system associated with reduced vibration detection (vibration perception threshold ≥25 V), estimated using a quantitative sensory testing device.

RESEARCH DESIGN AND METHODS—A Markov model was constructed for a hypothetical cohort of people with DPN. The model was run over a 10-year period using Monte Carlo simulations to estimate disease progression, predicted costs, and complications according to vibration detection levels.

RESULTS—The average individual with reduced vibration detection incurs approximately five times more direct medical costs for foot ulcer and amputations, yields 0.18 fewer quality-adjusted life-years, and lives for ∼2 months less than an average individual with normal vibration detection.

CONCLUSIONS—The treatment of foot ulceration and amputation is time-consuming and expensive. If individuals with reduced vibration detection could be identified, then preventative care could be concentrated on those patients, potentially saving valuable resources and improving health outcomes.
A Descriptive and Comparative Study of the Prevalence of Depressive and Anxiety Disorders in Low-Income Adults With Type 2 Diabetes and Other Chronic Illnesses
Authors: Thomas Janet , Jones Glenn , Scarinci Isabel , Brantley Phillip
Published: March 2007

OBJECTIVE—To determine whether type 2 diabetes contributes to the presence of depressive and anxiety disorder diagnoses in low-income adults with hypertension, asthma, and/or arthritis.

RESEARCH DESIGN AND METHODS—Using a cross-sectional design, this study administered a structured diagnostic interview to low-income primary care patients diagnosed with type 2 diabetes, hypertension, arthritis, and asthma, as well as to those with no chronic illness (n = 326), to determine the 12-month prevalence of depressive and anxiety disorders. A logistic regression (LR) model was used to assess whether a diagnosis of depression and/or anxiety was associated with type 2 diabetes after adjusting for known risk factors.

RESULTS—A high prevalence rate of depressive and/or anxiety disorders was found in the total sample (29%) and in all three illness groups: type 2 diabetes (36%), other chronic illnesses (24%), and no chronic illness (31%). Using LR, a main effect was detected for illness group when age and education were controlled (χ2 = 22.66, df 4, P = 0.000). Specifically, the odds of occurrence of a depressive and/or anxiety disorder in those with comorbid type 2 diabetes were twice that in the nondiabetic, chronically ill comparison group (odds ratio 2.26, 95% CI 1.28–4.01, P = 0.005).

CONCLUSIONS—These results suggest a positive contribution of type 2 diabetes to increased rates of depressive and/or anxiety disorders in patients with hypertension, asthma, and/or arthritis and support prior research that type 2 diabetes may serve as an indicator of depression and anxiety in low-income adults treated in primary care clinics.
Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes
Authors: Wang Ying , Ng Maggie C.Y. , Lee Shao-Chin , So Wing-Yee , Tong Peter C.Y. , Cockram Clive S. , Critchley Julian A.J.H. , Chan Juliana C.N.
Published: March 2007

OBJECTIVE—We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA)n microsatellite and a C/T polymorphism at the 5′ region of the aldose reductase gene (ALR2) in a consecutive cohort of 738 Chinese type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66 had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin excretion rate (AER) ≥20 μg/min and albumin-to-creatinine ratio ≥3.5 mg/mmol in two urine collections. Retinopathy was defined by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA)n and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with BfaI, respectively.

RESULTS—In the whole cohort, patients with diabetic retinopathy (n = 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy (n = 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications. The z+6 carriers of the (CA)n polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy (n = 551) (4.3 vs. 9.3%, P = 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 ×/÷ 7.2 vs. 21.9 ×/÷ 6.9 μg/min, P = 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with <5 years disease duration. The group with both diabetic nephropathy and retinopathy had higher frequencies of the z-2 allele (25.7 vs. 16.9%, P = 0.03) and T allele (26.4 vs. 18.5%, P = 0.04) and a lower frequency of the z+6 allele (1.7 vs. 5.5%, P = 0.054) than the uncomplicated group. Multiple logistic regression analysis confirmed that z-2 carrying (odds ratio 2.6, 95% CI 1.20–5.83, P = 0.02) and CT/TT genotypes (OR 2.5, 95% CI 1.19–5.19, P = 0.02) were independent predictors for both diabetic nephropathy and retinopathy.

CONCLUSIONS—Chinese type 2 diabetic patients exhibited phenotypic differences in terms of risk factors for both diabetic nephropathy and diabetic retinopathy. Both the z-2 allele of (CA)n polymorphism and T allele of ALR2 were independently associated with severe diabetic microvascular complications.
Prevalence of Diagnosed Diabetes Among African-American and Non-Hispanic White Youth, 1999
Authors: Oeltmann John E. , Liese Angela D. , Heinze Howard J. , Addy Cheryl L. , Mayer-Davis Elizabeth J.
Published: March 2007

OBJECTIVE—To document diabetes prevalence among African-American and non-Hispanic white youth in a two-county region in South Carolina.

RESEARCH DESIGN AND METHODS—We conducted a population-based surveillance effort to identify case subjects aged 0–18.9 years with a physician diagnosis of diabetes residing in a two-county region in 1999. Case subjects were ascertained from hospitals, the sole office of pediatric endocrinology, and several smaller sources. Case subjects were classified according to the diagnosis made by a pediatric endocrinologist. As a completeness check, eight randomly selected physicians were queried for eligible case subjects. Capture-recapture provided an additional measure of completeness. Prevalence estimates used U.S. 2000 Census data for the two-county denominator.

RESULTS—Crude total diabetes prevalence was 1.7 cases per 1,000 youth and similar between African-American and non-Hispanic white youth. Among younger youth (0–9.9 years), non-Hispanic white total prevalence was 1.1 per 1,000 and African-American prevalence was 0.6 per 1,000. Among older youth (10.0–18.9 years), non-Hispanic white total prevalence was 2.5 per 1,000 and African-American prevalence was 3.1 per 1,000. Type 2 diabetes was only confirmed among older prevalent cases. Ascertainment completeness was estimated to be 98%.

CONCLUSIONS—Our estimates suggest that total diabetes prevalence among non-Hispanic white youth is similar to rates observed over 20 years ago. Among African-American youth, the difference in prevalence noted between younger and older age-groups was notably greater than that observed among the non-Hispanic white youth, potentially reflecting a more marked increase in diabetes incidence with age.
Association Between Number of Physician Visits and Influenza Vaccination Coverage Among Diabetic Adults With Access to Care
Authors: Egede Leonard E.
Published: March 2007

OBJECTIVE—The proportion of diabetic adults that receives the influenza vaccine is less than ideal. This study determined the relationship between the number of physician visits in the previous 12 months and the likelihood of influenza vaccination among diabetic adults with access to care.

RESEARCH DESIGN AND METHODS—Data on 1,807 diabetic adults with access to care in the 1999 National Health Interview Survey (NHIS) were analyzed. Prevalence of influenza vaccination was determined by number of physician visits. Logistic regression was used to determine the independent association between number of physician visits and influenza vaccination coverage, controlling for age, sex, race/ethnicity, education, income, employment census region, and comorbidity. STATA was used for analyses to account for the complex sampling design of NHIS.

RESULTS—Overall, 56% of subjects received the influenza vaccine. Proportions vaccinated by number of physician visits were as follows: 35% (no visit), 47% (1–3 visits), 58% (4–9 visits), and 61% (≥10 visits). Compared with people with no physician visit, people with 4–9 visits (odds ratio [OR] 2.61) and ≥10 visits (2.96) were significantly more likely to be vaccinated. However, after controlling for covariates, only people with ≥10 visits (2.34) were significantly more likely to be vaccinated.

CONCLUSIONS—In this nationally representative sample, repeated physician visits by diabetic adults with access to care were associated with only modest increases in influenza vaccination coverage. In adjusted analysis, odds of influenza vaccination were not significantly associated with number of physician visits, except in people with ≥10 visits.
No Hypoglycemia After Subcutaneous Administration of Glucagon-Like Peptide-1 in Lean Type 2 Diabetic Patients and in Patients With Diabetes Secondary to Chronic Pancreatitis
Authors: Knop Filip K. , Vilsbøll Tina , Larsen Steen , Madsbad Sten , Holst Jens J. , Krarup Thure
Published: March 2007

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 ± 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity.

RESEARCH DESIGN AND METHODS—Eight lean type 2 diabetic patients (group 1) aged 60 years (range 50–72) with BMI 23.1 kg/m2 (20.3–25.5) and HbA1c 8.0% (6.9–11.4) and eight patients with type 2 diabetes secondary to chronic pancreatitis (group 2) aged 52 years (41–62) with BMI 21.9 kg/m2 (17.6–27.3) and HbA1c 7.8% (6.2–12.4) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body wt. Then, 15 min later, at the time of peak GLP-1 concentration, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. HOMA (mean ± SEM) showed insulin resistance amounting to 1.9 ± 0.3 and 1.7 ± 0.5 in the two groups, respectively.

RESULTS—In both groups, PG decreased rapidly and stabilized at 7.5 mmol/l (range 3.9–10.1) and 7.2 mmol/l (3.1–10.9) in groups 1 and 2, respectively, after 90 min. Neither symptoms of hypoglycemia nor biochemical hypoglycemia were observed in any patient.

CONCLUSIONS—We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.
Microvascular Complications at Time of Diagnosis of Type 2 Diabetes Are Similar Among Diabetic Patients Detected by Targeted Screening and Patients Newly Diagnosed in General Practice
Authors: Spijkerman Annemieke M.W. , Dekker Jacqueline M. , Nijpels Giel , Adriaanse Marcel C. , Kostense Piet J. , Ruwaard Dirk , Stehouwer Coen D.A. , Bouter Lex M. , Heine Robert J.
Published: March 2007

OBJECTIVE—To investigate whether screening-detected diabetic patients differ from diabetic patients newly diagnosed in general practice with regard to the presence of microvascular complications.

RESEARCH AND DESIGN METHODS—Diabetic patients, identified by a population-based targeted screening procedure consisting of a screening questionnaire and a fasting capillary whole-blood glucose measurement followed by diagnostic testing, were compared with patients newly diagnosed with diabetes in general practice. Retinopathy was assessed with fundus photography, impaired foot sensitivity was assessed with Semmes-Weinstein monofilaments, and the presence of microalbuminuria was measured by means of the albumin-to-creatinine ratio (ACR).

RESULTS—A total of 195 screening-detected type 2 diabetic patients and 60 patients newly diagnosed in general practice participated in the medical examination. The prevalence of retinopathy was higher in screening-detected type 2 diabetic patients than in patients newly diagnosed in general practice, but not significantly higher. The prevalence of retinopathy was 7.6% (95% CI 4.6–12.4) in screening-detected type 2 diabetic patients and 1.9% (0.3–9.8) in patients newly diagnosed in general practice. The prevalence of impaired foot sensitivity was similar in both groups, 48.1% (40.9–55.3) and 48.3% (36.2–60.7), respectively. The ACR was 0.61 (interquartile range 0.41–1.50) in screening-detected type 2 diabetic patients and 0.99 (0.53–2.49) in patients newly diagnosed in general practice. The difference in prevalence of microalbuminuria was not statistically significant. The prevalence of microalbuminuria was 17.2% (95% CI 12.5–23.2) and 26.7% (17.1–39.0) in screening-detected type 2 diabetic patients and patients newly diagnosed in general practice, respectively.

CONCLUSIONS—Targeted screening for type 2 diabetes (with a screening questionnaire as a first step) resulted in the identification of previously undiagnosed diabetic patients with a considerable prevalence of microvascular complications.
Impact of Metabolic Control and Serum Lipids on the Concentration of Advanced Glycation End Products in the Serum of Children and Adolescents With Type 1 Diabetes, as Determined by Fluorescence Spectroscopy and Nε-(Carboxymethyl)Lysine ELISA
Authors: Galler Angela , Müller Grit , Schinzel Reinhard , Kratzsch Juergen , Kiess Wieland , Münch Gerald
Published: March 2007

OBJECTIVE—Advanced glycation end products (AGEs) are a complex and heterogenous group of proteins that are formed by nonenzymatic glycation in a series of reactions. It is hypothesized that they may play a role in the pathogenesis of diabetes-related complications; at present, however, their exact biological role is scarcely understood. Clinical studies so far have shown that serum levels of AGEs are correlated with clinical stages of diabetes complications such as retinopathy and nephropathy. This study was performed in children and adolescents with type 1 diabetes to examine the putative role of serum AGEs in respect to metabolic control and diabetes complications in relation to a number of clinical and laboratory parameters.

RESEARCH DESIGN AND METHODS—We studied 99 children and adolescents up to the age of 20 years with type 1 diabetes and 60 control subjects. Serum levels of AGEs were measured with two different methods [fluorescence spectroscopy and Nε-(carboxymethyl)lysine (CML) enzyme-linked immunosorbent assay] and correlated with clinical data, such as age, diabetes duration, BMI, and long-term metabolic control determined by HbA1c, and laboratory parameters, such as serum lipids.

RESULTS—Serum levels of fluorescent AGEs, but not of CML-AGEs, in children and adolescents with type 1 diabetes were significantly higher compared with control subjects. There was an age-dependent increase of fluorescent AGEs in children and adolescents with diabetes that was not seen in healthy children and adolescents. Levels of fluorescent AGEs in patients with diabetes between 13 and 16 years of age correlated positively with HbA1c levels. No significant association between levels of AGEs and diabetes duration was found. Children and adolescents with diabetes and high serum triglycerides had significantly higher serum levels of fluorescent AGEs. Children and adolescents with diabetes between the age of 13 and 16 years with high levels of LDL had significantly higher levels of fluorescent AGEs.

CONCLUSIONS—In this study we demonstrated a clear age-dependent increase of fluorescent AGEs but not of CML-AGEs in children and adolescents with diabetes type 1. Moreover we showed a strong association between serum AGEs and serum triglycerides and cholesterol. The observed effect may be caused by a loss of optimal regulation of lipid metabolism. It could suggest a link between triglycerides and formation of AGEs. This new and interesting finding and its impact on metabolic control and the development of diabetes complications should be examined in the future.
Sympathetic Vasomotor Response of the Radial Artery in Patients With Diabetic Foot Syndrome
Authors: Eicke Bernhard M. , Bauer Julian , Mink Susanne , Kuhl Valerio , Hlawatsch Alexander , Küstner Ernst , Victor Anja
Published: March 2007

OBJECTIVE—Neurophysiological assessment of the peripheral autonomic system is characterized by various limitations. An alternative approach to laser Doppler and venous plethymography is the assessment of the sympathetic vasomotor response of the radial artery obtained by continuous wave Doppler sonography. Nomogram data have been established and demonstrate the temporary disappearance of diastolic flow after coughing or deep inspiration.

RESEARCH DESIGN AND METHODS—We assessed the sympathetic vasomotor response in 25 patients (mean age 64 years, range 43–76) with diabetic foot syndrome. The Doppler data were correlated with nerve conduction studies of the median and peroneal nerve, the extent of radiologically diagnosed media sclerosis, and compared with nomogram values (n = 41).

RESULTS—Although similar mean flow velocities were found under baseline conditions, the flow pattern was characterized by higher pulsatility in the diabetic group (resistance index [RI] 1.1 vs. 0.7). No significant difference in RI was observed after coughing. The latency of onset of the response was prolonged (2.1 vs. 1.5 s), while the duration of the response did not differ (18 vs. 15 s). Only the nerve conduction velocity of the peroneal nerve correlated inversely with the RI. The extent of radiologically proven calcification tended to correlate with the pulsatility of the baseline signal and the response latencies.

CONCLUSIONS—The data obtained by this study suggest the concurrent existence of reduced vessel elasticity due to media sclerosis and dysfunction of the autonomic vasomotor system.
Improvement in Diabetes Care of Underinsured Patients Enrolled in Project Dulce
Authors: Philis-Tsimikas Athena , Walker Chris , Rivard Lisa , Talavera Gregory , Reimann Joachim O.F. , Salmon Michelle , Araujo Rachel
Published: March 2007

OBJECTIVE—To improve clinical diabetes care, patient knowledge, and treatment satisfaction and to reduce health-adverse culture-based beliefs in underserved and underinsured populations with diabetes.

RESEARCH DESIGN AND METHODS—A total of 153 high-risk patients with diabetes recruited from six community clinic sites in San Diego County, California were enrolled in a nurse case management (NCM) and peer education/empowerment group. Baseline and 1-year levels of HbA1c, lipid parameters, systolic and diastolic blood pressure, knowledge of diabetes, culture-based beliefs in ineffective remedies, and treatment satisfaction were prospectively measured. The NCM and peer education/empowerment group was compared with 76 individuals in a matched control group (CG) derived from patients referred but not enrolled in Project Dulce.

RESULTS—After 1 year in Project Dulce, the NCM and peer education/empowerment group had significant improvements in HbA1c (12.0–8.3%, P < 0.0001), total cholesterol (5.82–4.86 mmol/l, P < 0.0001), LDL cholesterol (3.39–2.79 mmol/l, P < 0.0001), and diastolic blood pressure (80–76 mmHg, P < 0.009), which were significantly better than in the CG, in which no significant changes were noted. Accepted American Diabetes Association standards of diabetes care, knowledge of diabetes (P = 0.024), treatment satisfaction (P = 0.001), and culture-based beliefs (P = 0.001) were also improved.

CONCLUSIONS—A novel, culturally appropriate, community-based, nurse case management/peer education diabetes care model leads to significant improvement in clinical diabetes care, self-awareness, and understanding of diabetes in underinsured populations.
One-Year Glycemic Control With a Sulfonylurea Plus Pioglitazone Versus a Sulfonylurea Plus Metformin in Patients With Type 2 Diabetes
Authors: Hanefeld Markolf , Brunetti Paolo , Schernthaner Guntram H. , Matthews David R. , Charbonnel Bernard H. ,   on behalf of the QUARTET Study Group
Published: March 2007

OBJECTIVE—The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes.

RESEARCH DESIGN AND METHODS—In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA1c at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured.

RESULTS—HbA1c was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm −1.3 μIU/ml; metformin arm −0.8 μIU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (−16 vs. −9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group.

CONCLUSIONS—Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes.