bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrovascular Risk and Diagnostic Criteria for Type 2 Diabetes
Authors: Jesudason David R. , Dunstan Kerrie , Leong Darryl , Wittert Gary A.
Published: March 2007

OBJECTIVE—The use of fasting plasma glucose (FPG) level ≥7.0 mmol/l leads to underdiagnosis of type 2 diabetes compared with the oral glucose tolerance test (OGTT). The OGTT is of limited use for population screening. Most of the increase in cardiovascular risk in relation to increasing blood glucose occurs before the threshold at which the diagnosis of type 2 diabetes is made. The aim of this study was to evaluate the use of HbA1c and FPG as predictors of type 2 diabetes and cardiovascular risk and, accordingly, to develop a rational approach to screening for abnormalities of glucose tolerance.

RESEARCH DESIGN AND METHODS—OGTT and measurement of HbA1c and FPG levels were performed in 505 subjects screened for type 2 diabetes. Anthropomorphic measurements were obtained. A cardiovascular risk factor questionnaire was completed.

RESULTS—The subjects were aged 19–88 years (mean 53.8). The incidence of type 2 diabetes was 10.4% based on the OGTT and 4% based on an FPG level ≥7.0 mmol/l. Using high-performance liquid chromatography (HPLC), HbA1c of <4.7 and ≥6.2% predicted with certainty the absence or presence of type 2 diabetes as defined by the OGTT. The corresponding cutoffs were <5.0 and ≥6.8% for HbA1c (DCA2000 HPLC device; Bayer Diagnostics, Mulgrave, Australia) and <4.7 and ≥6.4 mmol/l for FPG. However, 75–85% of subjects in each case had intermediate values, which were therefore nondiagnostic. Cardiovascular risk increased at least 2.2 times at an HbA1c level ≥6.2% (by HPLC), 1.8–2.2 times at an HbA1c level of 5.6–6.1% (by HPLC), 2 times at an FPG level ≥6.4 mmol/l, and 1.7–1.9 times at an FPG level of 5.6–6.3 mmol/l.

CONCLUSIONS—Measurement of FPG and HbA1c levels will diagnose or exclude type 2 diabetes with certainty in a minority (15%) of people. There is a continuous relationship between FPG and HbA1c and cardiovascular risk. Accordingly, we propose that there is a rational basis for using either FPG and HbA1c for purposes of screening and assigning risk. Individuals with an HbA1c level of 5.6–6.1% and an FPG level of 5.6–6.3 mmol/l are at greatest risk for cardiovascular disease and should be targeted for further evaluation. An algorithm outlining a cost-effective approach is presented.
Work Stress and Low Sense of Coherence Is Associated With Type 2 Diabetes in Middle-Aged Swedish Women
Authors: Agardh Emilie E. , Ahlbom Anders , Andersson Tomas , Efendic Suad , Grill Valdemar , Hallqvist Johan , Norman Anders , Östenson Claes-Göran
Published: March 2007

OBJECTIVE—The risk of type 2 diabetes is suggested to be increased for individuals exposed to stress. We analyzed the association of work stress by high demands, low decision latitude, and job strain (combination of high demands and low decision latitude) with type 2 diabetes. We also studied low sense of coherence (SOC) (a factor for successful coping with stressors) in association with type 2 diabetes. Finally, we investigated the combination of SOC and demands or SOC and decision latitude in association with the disease.

RESEARCH DESIGN AND METHODS—This cross-sectional study recruited 4,821 healthy Swedish women (aged 35–56 years) residing in five municipalities in the Stockholm area. An oral glucose tolerance test identified 52 women with type 2 diabetes. Relative risks (RRs) with 95% CIs were estimated in a logistic multiple regression analysis.

RESULTS—No association was found between high demands and type 2 diabetes (RR 1.1 [CI 0.5–2.2]). Low decision latitude was associated with type 2 diabetes with a RR of 2.2 (1.0–4.8). The RR of type 2 diabetes with low SOC was 3.7 (1.2–11.2). The combination of low SOC and low decision latitude was associated with type 2 diabetes with a RR of 2.6 (1.2–5.7). Homeostasis model assessment revealed an association of 4.2 (1.2–15.0) between low SOC and insulin resistance.

CONCLUSIONS—This study provided new evidence that stress factors such as low decision latitude at work and low SOC were associated with type 2 diabetes in middle-aged Swedish women.
Smoking and Progression of Diabetic Nephropathy in Type 1 Diabetes
Authors: Hovind Peter , Rossing Peter , Tarnow Lise , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—Cigarette smoking contributes to development of diabetic nephropathy. However, long-term studies on the effect of smoking on decline in kidney function in diabetic nephropathy are lacking. We assessed the impact of smoking on progression of diabetic nephropathy in type 1 diabetic patients enrolled in a prospective observational cohort study started in 1983.

RESEARCH DESIGN AND METHODS—We identified all albuminuric type 1 diabetic patients (n = 301) followed for at least 3 years, median (range) 7 years (3–14), who underwent at least yearly measurement of glomerular filtration rate (GFR) by the 51Cr-EDTA plasma clearance technique (n = 8, range 3–24). In total, 192 men and 109 women were included (age [mean ± SD] 36 ± 11 years, duration of diabetes 22 ± 8 years); 271 patients were treated with antihypertensive drugs, predominantly ACE inhibitors in 179 patients. Patients were classified as smokers if they smoked more than one cigarette per day during a portion of or the entire observation period. Blood pressure, albuminuria, HbA1c, and serum cholesterol were measured every 3–4 months during the study.

RESULTS—In all 301 patients, the mean (SE) rate of decline in GFR (ΔGFR) was 4.0 (0.2) ml · min−1 · year−1 during the investigation period. No difference in Δ GFR was demonstrated between nonsmokers (n = 94), ΔGFR 4.5 (0.4), ex-smokers (n = 31), ΔGFR 3.1 (0.7), and smokers (n = 176), ΔGFR 3.9 (0.3) ml · min−1 · year−1, respectively (NS). Adjustment for other risk factors for progression of diabetic nephropathy did not alter the results: smoking was not associated with ΔGFR, whereas blood pressure, albuminuria, HbA1c, and serum cholesterol were demonstrated to be independent progression promoters.

CONCLUSIONS—In our study, smoking was not associated with decline in kidney function in type 1 diabetic patients with diabetic nephropathy.
Analysis of Metabolic Parameters as Predictors of Risk in the RENAAL Study
Authors: Appel Gerald B. , Radhakrishnan Jai , Avram Morrell M. , DeFronzo Ralph A. , Escobar-Jimenez Fernando , Campos M.M. , Burgess Ellen , Hille Darcy A. , Dickson Tania Z. , Shahinfar Shahnaz , Brenner Barry M. ,   for the RENAAL Study Investigators
Published: March 2007

OBJECTIVE—Metabolic factors such as glycemic control, hyperlipidemia, and hyperkalemia are important considerations in the treatment of patients with type 2 diabetes and nephropathy. In the RENAAL (Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan) study, losartan reduced renal outcomes in the patient population. This post hoc analysis of the RENAAL study reports the effects of losartan on selected metabolic parameters and assesses the relationship between baseline values of metabolic parameters and the primary composite end point or end-stage renal disease (ESRD).

RESEARCH DESIGN AND METHODS—Glycemic control (HbA1c) and serum lipid, uric acid, and potassium levels were compared between the losartan and placebo groups over time, and baseline levels were correlated with the risk of reaching the primary composite end point (doubling of serum creatinine, ESRD, or death) or ESRD alone.

RESULTS—Losartan did not adversely affect glycemic control or serum lipid levels. Losartan-treated patients had lower total (227.4 vs. 195.4 mg/dl) and LDL (142.2 vs. 111.7 mg/dl) cholesterol. Losartan was associated with a mean increase of up to 0.3 mEq/l in serum potassium levels; however, the rate of hyperkalemia-related discontinuation was similar between the placebo and losartan groups. Univariate analysis revealed that baseline total and LDL cholesterol and triglyceride levels were associated with increased risk of developing the primary composite end point. Similarly, total and LDL cholesterol were also associated with increased risk of developing ESRD.

CONCLUSIONS—Overall, losartan was well tolerated by patients with type 2 diabetes and nephropathy and was associated with a favorable effect on the metabolic profile of this population.
The Prevalence of and Factors Associated With Diabetic Retinopathy in the Australian Population
Authors: Tapp Robyn J. , Shaw Jonathan E. , Harper C. Alex , de Courten Maximilian P. , Balkau Beverley , McCarty Daniel J. , Taylor Hugh R. , Welborn Timothy A. , Zimmet Paul Z. ,   on behalf of the AusDiab Study Group
Published: March 2007

OBJECTIVE—To determine the prevalence and factors associated with diabetic retinopathy in the Australian population and to estimate the time difference between disease onset and clinical diagnosis of type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Australian Diabetes, Obesity and Lifestyle study (AusDiab) included 11,247 adults aged ≥25 years in 42 randomly selected areas of Australia. Retinopathy was assessed in participants identified as having diabetes (based on self-report and oral glucose tolerance test), impaired fasting glucose, and impaired glucose tolerance and in a random sample with normal glucose tolerance. Data were available for 2,177 participants.

RESULTS—Overall, 15.3% of those with diabetes had retinopathy. The prevalence of retinopathy was 21.9% in those with known type 2 diabetes (KDM) and 6.2% in those newly diagnosed (NDM). The prevalence of proliferative diabetic retinopathy (PDR) was 2.1% in those with KDM. No cases of PDR were found in those with NDM. Untreated vision threatening retinopathy (presence of PDR or macular edema) was present in 1.2% (n = 4). Factors associated with retinopathy were duration of diabetes, HbA1c, and systolic blood pressure. Using linear extrapolation of the prevalence of retinopathy with diabetes duration, the onset of diabetes in this population was approximately the time of diagnosis.

CONCLUSIONS—This is one of the first national studies of diabetic retinopathy in a developed country. The prevalence of retinopathy was similar to that in other population-based studies. Vision threatening retinopathy was relatively rare; however, four untreated cases were identified. Regular screening for diabetic retinopathy and more aggressive management of modifiable risk factors could reduce the numbers of people who develop vision-threatening retinopathy.
Identification and Management of Diabetic Nephropathy in the Diabetes Clinic
Authors: Craig Kathrine J. , Donovan Kieron , Munnery Margaret , Owens David R. , Williams John D. , Phillips Aled O.
Published: March 2007

OBJECTIVE—To examine the prevalence and management of diabetic nephropathy in a diabetes clinic.

RESEARCH DESIGN AND METHODS—Characteristics of nephropaths identified by existing screening practice (phase I, albuminuria >20 mg/l in three separate urine samples), were compared with those identified by a nurse-led management program (phase II, in which screening for nephropathy was based on albumin-to-creatinine ratio in a single random urine specimen).

RESULTS—In phase I, 644 patients attended a diabetes clinic over a 6-month period. Microalbuminuria results were available for 485 patients (75%). A total of 115 patients were identified as nephropaths (prevalence 17.8%). Of these patients, 91% had type 2 diabetes. During phase II, prospective analysis of urinary albumin-to-creatinine ratio was carried out in 880 patients over 8 months. A total of 174 patients were identified as nephropaths (prevalence 20%). Of these, 134 patients had been identified by existing screening protocols. Forty had no previous record of microalbuminuria and were therefore newly identified by prospective screening. Systolic blood pressure guidelines were met in only 31% of all known nephropaths and 26.5% of newly diagnosed nephropaths. Diastolic blood pressure guidelines were met in 36% of all known and 38% of newly diagnosed nephropaths. In the patient group of known nephropaths from phases I and II, 62% were prescribed ACE inhibitors (ACEIs) or angiotensin II receptor (AIIR) antagonists. In the newly identified nephropathy patient cohort from phase II, 48% used ACEIs or AIIR antagonists.

CONCLUSIONS—Introduction of a nurse-led management program significantly improved detection of nephropathy. We are currently evaluating its impact on clinical management.
Köbberling Type of Familial Partial Lipodystrophy
Authors: Herbst Karen L. , Tannock Lisa R. , Deeb Samir S. , Purnell Jonathan Q. , Brunzell John D. , Chait Alan
Published: March 2007

OBJECTIVE—The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought.

RESEARCH DESIGN AND METHODS—Fasting glucose, plasma lipids, leptin, HbA1c, and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes.

RESULTS—Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-γ.

CONCLUSIONS—FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease.
Significance of Microalbuminuria in Long-Duration Type 1 Diabetes
Authors: Arun Chankramath S. , Stoddart James , Mackin Paul , MacLeod Jean M. , New John P. , Marshall Sally M.
Published: March 2007

OBJECTIVE—The value of microalbuminuria (MA) in predicting renal disease and premature mortality in longer duration type 1 diabetes is unclear.

RESEARCH DESIGN AND METHODS—We followed 135 patients with long-standing type 1 diabetes (>30 years’ duration) over a 7-year period, recording albuminuria and other clinical variables. Vital status was ascertained and cause of death was recorded.

RESULTS—A total of 27 of 135 patients (20%) died during the follow-up period. Patients with MA (10 of 30, 33.3%) or proteinuria (5 of 6, 83.3%) at initial examination were more likely to die during follow-up than patients who had normal albumin excretion at baseline (12 of 99, 12%; χ2 for trend 21.9, P < 0.0001). The presence of abnormal albumin excretion and low BMI were independent risk factors of premature death. The causes of death were similar in patients with normal and abnormal urine albumin excretion. A total of 24.4% of initially normoalbuminuric survivors developed MA, and persistent proteinuria developed in 3.5%. Progressors had significantly higher albumin excretion rate at baseline compared with those who remained normoalbuminuric: 9.0 μg/min (3.8–18) vs. 4.0 μg/min (0.4–17.5); P < 0.001. A total of 21% of patients with MA at baseline reverted to normoalbuminuria, and persistent proteinuria developed in 32%. The likelihood of progression to persistent proteinuria was significantly greater in those with baseline MA compared with those with normal albumin excretion (P < 0.001).

CONCLUSIONS—Even in long-standing type 1 diabetes of >30 years’ duration, MA and proteinuria predict all-cause mortality. MA is a good predictor of persistent proteinuria.
Prenatal Growth, BMI, and Risk of Type 2 Diabetes by Early Midlife
Authors: Hyppönen Elina , Power Chris , Smith George Davey
Published: March 2007

OBJECTIVE—Small size at birth has been associated with increased risk of type 2 diabetes. Our aim was to evaluate how risk of diabetes associated with low birth weight is affected by accumulation of body mass from childhood to adulthood.

RESEARCH DESIGN AND METHODS—Subjects from the 1958 British birth cohort (born 3–9 March 1958) have been followed regularly since birth. In the survey at 41 years of age, 88 participants reported type 2 diabetes (n = 10,683).

RESULTS—Participants in whom diabetes developed weighed less at birth and had higher BMIs than the others. Birth weight (adjusted for gestational age and sex) was inversely related to risk of diabetes (odds ratio for 1-SD change 0.76, 95% CI 0.56–0.99). All diabetic participants in the lowest third of birth weight were in the highest third of weight gain by 23 years of age. An increased risk of diabetes was found for those in the lowest third of BMI at 7 years of age (2.84, 1.2–6.9), but diabetic participants in this group had excessive weight gain to 23 years of age. All but one diabetic participant in the highest third of childhood BMI remained in the highest third until 23 years of age. Risk of diabetes by BMI at 23 years of age was 22.9-fold (95% CI 12–42) for obese participants and 3.8-fold (2.1–6.9) for overweight participants compared with those of normal weight.

CONCLUSIONS—There was no increase in risk of diabetes for small size at birth without excessive postnatal weight gain. Adult obesity was the most important risk factor for type 2 diabetes developing by early midlife.
Risk Factors for Myocardial Infarction Case Fatality and Stroke Case Fatality in Type 2 Diabetes
Authors: Stevens Richard J. , Coleman Ruth L. , Adler Amanda I. , Stratton Irene M. , Matthews David R. , Holman Rury R.
Published: March 2007

OBJECTIVE—Patients with diabetes have a higher case fatality rate in myocardial infarction (MI) or stroke than those without diabetes: that is, MI and stroke are more often fatal if diabetes is present. We investigated whether the risk of MI or stroke being fatal in type 2 diabetes can be estimated using information available around the time diabetes is diagnosed.

RESEARCH DESIGN AND METHODS—Analyses were based on 674 cases of MI (351 fatal) that occurred in 597 of 5,102 U.K. Prospective Diabetes Study (UKPDS) patients for whom covariate data were available during a median follow-up of 7 years. Multivariate logistic regression was used to examine differences in risk factors, measured within 2 years of diagnosis of diabetes, between fatal and nonfatal MI. Similar analyses were performed for 234 strokes (48 fatal) that occurred in 199 patients.

RESULTS—Patients with fatal MI had higher HbA1c than those with nonfatal MI (odds ratio 1.17 per 1% HbA1c, P = 0.014). Patients with fatal stroke had higher HbA1c than those with nonfatal stroke (odds ratio 1.37 per 1% HbA1c, P = 0.007). Other risk factors for MI case fatality included increased age, blood pressure, and urine albumin level.

CONCLUSIONS—The risk of MI or stroke being fatal in type 2 diabetes is associated with risk factors, including HbA1c, measured many years before onset of MI or stroke. Equations have been added to the UKPDS Risk Engine to estimate likely case fatality rates in MI and stroke.
Antihypertensive Therapy and Incidence of Type 2 Diabetes
Authors: Padwal Raj , Laupacis Andreas
Published: March 2007

OBJECTIVE—To systematically review the available evidence examining the effects of the major antihypertensive drug classes on the incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Cochrane Controlled Trials Register, Medline, and Embase were searched for English-language case-control, cohort, and randomized controlled trials involving the major antihypertensive classes and reporting type 2 diabetes as an end point. Reference lists of original studies and narrative reviews were also hand searched. One reviewer (R.P.) performed the electronic searches. Both reviewers independently extracted data and assessed all potentially relevant studies for inclusion and methodological quality. Abstracts were not included, and unpublished studies were not sought.

RESULTS—One case-control study, 8 cohort studies, and 14 randomized controlled trials met inclusion criteria. No study examined diabetes incidence as a primary end point. Poor methodological quality limits the conclusions that can be drawn from most nonrandomized trials. Evidence from randomized studies is also potentially limited by several sources of bias, including treatment contamination and bias inherent in post hoc analyses. Data from the highest-quality studies suggest that diabetes incidence is unchanged or increased by thiazide diuretics and β-blockers and unchanged or decreased by ACE inhibitors, calcium channel blockers, and angiotensin receptor blockers.

CONCLUSIONS—The major antihypertensive classes may exert differential effects on diabetes incidence, although current data are far from conclusive. Ongoing placebo-controlled randomized trials involving potentially beneficial drug classes and examining diabetes incidence as a primary end point should provide more definitive evidence.
Adiponectin Concentrations in Sera From Patients With Type 2 Diabetes Are Negatively Associated With Sympathovagal Balance as Evaluated by Power Spectral Analysis of Heart Rate Variation
Authors: Wakabayashi Sadao , Aso Yoshimasa
Published: March 2007

OBJECTIVE—To investigate whether cardiac autonomic activity, particularly sympathovagal balance as estimated by power spectral analysis (PSA) of heart rate variation (HRV), is associated with serum adiponectin concentrations in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We studied 105 patients with type 2 diabetes (51 women and 54 men). Serum adiponectin concentrations were measured by sandwich enzyme-linked immunosorbent assay. HRV was determined automatically every 5 min over 24 h using Holter electrocardiographic recording. PSA of R-R intervals was performed using fast Fourier transformation. Low-frequency (both sympathetic and parasympathetic activities), high- frequency (pure parasympathetic activity), and the ratio of low-frequency-to-high-frequency power (LF-to-HF ratio), an index of sympathovagal balance, were used as indexes of cardiac autonomic activity.

RESULTS—We found no significant correlation between serum adiponectin and low-frequency or high-frequency power in patients with diabetes. Serum adiponectin concentration correlated negatively with the 24-h LF-to-HF ratio (r = −0.343, P = 0.0009) and creatinine clearance (r = −0.411, P < 0.0001). Serum adiponectin concentrations were significantly higher in patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria. In multivariate analysis controlling for sex, BMI, glycemic control, lipid profile, and renal function, serum adiponectin concentration showed an independent negative association with 24-h LF-to-HF ratio (β = −0.332, P = 0.020). Furthermore, sex, HDL cholesterol, and renal function retained significant influence on the serum adiponectin concentration in patients with diabetes.

CONCLUSIONS—Sympathovagal balance favoring relative sympathetic activation was associated with low serum concentrations of adiponectin in patients with type 2 diabetes.
Explanations for the High Risk of Diabetes-Related Amputation in a Caribbean Population of Black African Descent and Potential for Prevention
Authors: Hennis Anselm J.M. , Fraser Henry S. , Jonnalagadda Ramesh , Fuller John , Chaturvedi Nish
Published: March 2007

OBJECTIVE—Diabetes-related lower-extremity amputation (LEA) rates are elevated in blacks compared with whites in the U.S., but are lower in African Caribbeans in the U.K., whereas anecdotal reports suggest high rates in the Caribbean. We aimed to establish the incidence and risk factors for diabetes-related LEA in a Caribbean population.

RESEARCH DESIGN AND METHODS—We conducted an incident and prospective case-control study of case patients (individuals with diabetes having a LEA) and community-based control subjects (individuals with diabetes without a LEA) in Barbados, West Indies. Participants completed an interview and examination of risk factors for amputation, including footwear use.

RESULTS—The overall 1-year incidence of LEA (n = 223) was 173 per 105 population and 936 per 105 population with diabetes (557 per 105 for minor amputation and 379 per 105 for major amputation). Women had higher amputation rates than those reported in the Global Lower Extremity Amputation Study, apart from the U.S. Navajo population. Independent risk factors for all diabetes-related LEAs were poor footwear (odds ratio [OR] 2.71 [95% CI 1.23–5.97]), elevated GHb (1.40 per percent increase [1.26–1.57]), peripheral neuropathy (1.05 per volt increase [1.03–1.08]), and peripheral vascular disease.

CONCLUSIONS—Diabetes LEA rates in Barbados are among the highest in the world. Inadequate footwear independently tripled amputation risk. Education of professionals and patients, particularly about footwear and foot care, coupled with improved diabetes clinical care, is key to reducing amputation risk in this population.
The Impact of Abnormalities in IGF and Inflammatory Systems on the Metabolic Syndrome
Authors: Kaushal Kalpana , Heald Adrian H. , Siddals Kirk W. , Sandhu Manjinder S. , Dunger David B. , Gibson John M. , Wareham Nick J.
Published: March 2007

OBJECTIVE—Low plasma levels of IGF-I, particularly when coupled with low levels of the potentially inhibitory IGF binding protein (IGFBP)-1 and higher levels of C-reactive protein (CRP), have been implicated in the pathogenesis of metabolic syndrome X and cardiovascular disease. We report the relative contributions of IGFBP-1 and CRP to the occurrence of the metabolic syndrome in a healthy population cohort to establish the extent to which these factors may contribute to subsequent risk of cardiovascular disease.

RESEARCH DESIGN AND METHODS—The volunteers in the study were all participants in the Ely study, a continuing population-based cohort in Ely, Cambridgeshire, U.K. Of 839 individuals studied, 154 (18.4%) fulfilled criteria for the metabolic syndrome.

RESULTS—Subjects with the metabolic syndrome had lower IGFBP-1 (14.4 μg/l [95% CI 12.9–16.0] vs. 25.4 [24.1–26.7], P < 0.001) and higher CRP (1.9 mg/l [1.6–2.2] vs. 1.0 [0.9–1.1], P < 0.001). Logistic regression, adjusted for age, sex, fasting insulin, and IGF-I, demonstrated a striking 14-fold increased risk for the metabolic syndrome (odds ratio 14.1 [4.1–48.4], P < 0.001) in individuals with a CRP value in the highest tertile and IGFBP-1 levels below the median.

CONCLUSIONS—The combination of a high CRP concentration coupled with a low IGFBP-1 results in a dramatic increase in an individual’s risk of having the metabolic syndrome. Further elucidation of the biological processes linking the IGF and inflammatory systems may allow the identification of novel therapeutic targets for cardiovascular risk reduction.
Sympathetic and Parasympathetic Neuropathy Are Frequent in Both Type 1 and Type 2 Diabetic Patients
Authors: Freccero Carolin , Svensson Henry , Bornmyr Siv , Wollmer Per , Sundkvist Göran
Published: March 2007

OBJECTIVE—The aim of this study was to evaluate the frequency of sympathetic versus parasympathetic neuropathy among type 1 and type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—There were 43 patients with type 1 and 17 with type 2 diabetes who were investigated. Sympathetic nerve function was assessed by measurement of the vasoconstriction (VAC) index by laser Doppler perfusion imaging of a locally heated finger followed by indirect cooling. Parasympathetic nerve function was assessed by R-R interval variation during deep breathing as measured by the expiration/inspiration (E/I) ratio. Results were expressed as age-corrected z scores in SD; VAC index >1.64 SD and E/I ratio <−1.64 SD were considered abnormal.

RESULTS—VAC index was abnormal in 40% with type 1 and 41% with type 2 diabetes, whereas the E/I ratio was abnormal in 42% with type 1 and 65% with type 2 diabetes. There was a clear association between VAC index and E/I ratio among type 1 (rs = 0.525; P = 0.0002) but not among type 2 (rs = 0.10) diabetic patients. Among type 2 diabetic patients, the degree of dysfunction was most severe regarding parasympathetic function (P = 0.0167).

CONCLUSIONS—Sympathetic and parasympathetic neuropathy were frequent in both type 1 and type 2 diabetic patients. However, there was a difference between the two types of diabetes. Sympathetic and parasympathetic nerve functions correlated in type 1 but not in type 2 diabetic patients. The explanation for this discrepancy might be that parasympathetic nerve function was most severely affected among type 2 diabetic patients.
Health Literacy and Pregnancy Preparedness in Pregestational Diabetes
Authors: Endres Loraine K. , Sharp Lisa K. , Haney Elaine , Dooley Sharon L.
Published: March 2007

OBJECTIVE—We investigated the association between functional health literacy and markers of pregnancy preparedness in women with pregestational diabetes.

RESEARCH DESIGN AND METHODS—English- and Spanish-speaking pregnant women with pregestational diabetes were recruited. Women completed the Test of Functional Health Literacy in Adults (TOFHLA) short form and a questionnaire. A TOFHLA score of ≤30 was defined as low functional health literacy.

RESULTS—Of 74 women participating in the study, 16 (22%) were classified as having low functional health literacy. Compared with women with adequate health literacy, those with low health literacy were significantly more likely to have an unplanned pregnancy (P = 0.02) and significantly less likely to have either discussed pregnancy ahead of time with an endocrinologist or obstetrician (P = 0.01) or taken folic acid (P = 0.001).

CONCLUSIONS—The results of this study suggest that low functional health literacy among women with pregestational diabetes is associated with several factors that may adversely impact birth outcomes.
The Effect of the PREMIER Interventions on Insulin Sensitivity
Authors: Ard Jamy D. , Grambow Steve C. , Liu Di , Slentz Cris A. , Kraus William E. , Svetkey Laura P.
Published: March 2007

OBJECTIVE—This ancillary study of PREMIER sought to determine the effects on insulin sensitivity of a comprehensive behavioral intervention for hypertension with and without the Dietary Approaches to Stop Hypertension (DASH) dietary pattern.

RESEARCH DESIGN AND METHODS— Participants were assigned to one of three nonpharmacologic interventions for blood pressure (group A, advice only; group B, established; and group C, established plus DASH). The established intervention included weight loss, reduced sodium intake, increased physical activity, and moderate alcohol intake; the DASH dietary pattern was added to the established intervention for those in group C. The DASH dietary pattern is high in fruits, vegetables, and low-fat dairy products while being lower in total fat, saturated fat, and cholesterol. It is abundant in nutrients such as magnesium, calcium, and protein, which have been associated with improved insulin sensitivity. Insulin sensitivity was measured at baseline and at 6 months using the frequently sampled intravenous glucose tolerance test with minimal model analysis.

RESULTS—Both intervention groups decreased total calories, percentage of calories from fat, and sodium intake to similar levels, with similar amounts of energy expenditure and weight loss. Covariate differences seen only in group C included increased intake of protein, potassium, calcium, and magnesium. Compared with control subjects, insulin sensitivity improved significantly only in group C, from 1.96 to 2.95 (P = 0.047). Group B did have a significant decrease in fasting insulin and glucose, but the changes in insulin sensitivity did not reach statistical significance when compared with control subjects.

CONCLUSIONS—These results suggest that including the DASH dietary pattern as part of a comprehensive intervention for blood pressure control enhances insulin action beyond the effects of a comprehensive intervention that does not include DASH.
A Comparison of Self-Reported Energy Intake With Total Energy Expenditure Estimated by Accelerometer and Basal Metabolic Rate in African-American Women With Type 2 Diabetes
Authors: Samuel-Hodge Carmen D. , Fernandez Louise M. , Henríquez-Roldán Carlos F. , Johnston Larry F. , Keyserling Thomas C.
Published: March 2007

OBJECTIVE—This study assesses the validity of dietary data from African-American women with type 2 diabetes by comparing reported energy intake (EI) with total energy expenditure (TEE) estimated by an accelerometer and basal metabolic rate (BMR).

RESEARCH DESIGN AND METHODS—EI of 200 African-American women was assessed by three telephone-administered 24-h diet recalls using a multiple-pass approach. Physical activity was measured over a 7-day period by accelerometer, which also provided an estimate of TEE. Underreporting of EI was determined by using cutoffs for EI-to-TEE and EI-to-BMR ratios.

RESULTS—Participants, on average, were 59 years of age, with a BMI of 35.7, 10.5 years of diagnosed diabetes, and 10.7 years of education. Mean EI was 1,299 kcal/day; mean EI-to-TEE and EI-to-BMR ratios were 0.65 and 0.88, respectively. Among the 185 subjects with complete dietary data, 81% (n = 150) were classified as energy underreporters using the EI-to-TEE ratio cutoff; 58% (n = 107) were classified as energy underreporters using the EI-to-BMR ratio. Energy underreporters had significantly lower reported fat, higher protein, but similar carbohydrate intakes compared with non-underreporters. The EI-to-TEE ratio was not significantly associated with any demographic variables or following a diet for diabetes, but it was inversely associated with BMI (r = −0.37, P < 0.0001). In a multivariate model, demographic variables, BMI, and following a diet for diabetes explained 16% of the variance in the EI-to-TEE ratio, with the latter two variables being the only significant predictors (inversely associated).

CONCLUSIONS—Widespread energy underreporting among this group of overweight African-American women with type 2 diabetes severely compromised the validity of self-reported dietary data.
Relationship Between GHb Concentration and Erythrocyte Survival Determined From Breath Carbon Monoxide Concentration
Authors: Virtue Mark A. , Furne Julie K. , Nuttall Frank Q. , Levitt Michael D.
Published: March 2007

OBJECTIVE—Subjects with decreased erythrocyte survival have an unusually low GHb percentage. The goal of this study was to determine whether hyperglycemia, as reflected by GHb percentage, is associated with decreased erythrocyte survival.

RESEARCH DESIGN AND METHODS—Erythrocyte survival was quantitated in 23 subjects with type 2 diabetes, and these values were correlated with the subjects’ GHb percentage. Erythrocyte survival was determined from the difference between the subjects’ alveolar carbon monoxide (CO) concentration and atmospheric CO concentration. Reticulocyte counts were obtained in 16 subjects.

RESULTS—Although the vast majority of the subjects had erythrocyte life spans that fell within the normal range (123 ± 23 days), there was a highly significant inverse correlation (r = −0.66, P < 0.01) between life span and GHb percentage, with an average decline in life span of 6.9 days for each 1% rise in GHb. The reticulocyte count inversely correlated with erythrocyte life span (r = −0.77, P < 0.01).

CONCLUSIONS—Hyperglycemia, as evidenced by high GHb percentage, is associated with an appreciable decrease in erythrocyte life span. Because GHb appears to be formed over the lifetime of the erythrocyte, this decreased erythrocyte survival suggests that high GHb percentages may systematically underestimate the true degree of hyperglycemia.
Eighteen Years of Fair Glycemic Control Preserves Cardiac Autonomic Function in Type 1 Diabetes
Authors: Larsen Jakob R. , Sjøholm Hans , Berg Tore J. , Sandvik Leiv , Brekke Magne , Hanssen Kristian F. , Dahl-Jørgensen Knut
Published: March 2007

OBJECTIVE—To study the association between 18 years of mean HbA1c and cardiac autonomic function in type 1 diabetic patients having used intensive insulin treatment.

RESEARCH DESIGN AND METHODS—A total of 39 patients with type 1 diabetes were followed during 18 years, and HbA1c was measured yearly. At 18 years follow-up heart rate variability (HRV) measurements were used to assess cardiac autonomic function. Standard cardiac autonomic tests during normal breathing, deep breathing, the Valsalva maneuver, and the tilt test were performed. Maximal heart rate increase during exercise electrocardiogram and minimal heart rate during sleep were also used to describe cardiac autonomic function.

RESULTS—We present the results for patients with mean HbA1c <8.4% (two lowest HbA1c tertiles) compared with those with HbA1c ≥8.4% (highest HbA1c tertile). All of the cardiac autonomic tests were significantly different in the high- and the low-HbA1c groups, and the most favorable scores for all tests were seen in the low-HbA1c group. In the low-HbA1c group, the HRV was 40% during deep breathing, and in the high-HbA1c group, the HRV was 19.9% (P = 0.005). Minimal heart rate at night was significantly lower in the low-HbA1c groups than in the high-HbA1c group (P = 0.039). With maximal exercise, the increase in heart rate was significantly higher in the low-HbA1c group compared with the high-HbA1c group (P = 0.001).

CONCLUSIONS—Mean HbA1c during 18 years was associated with cardiac autonomic function. Cardiac autonomic function was preserved with HbA1c <8.4%, whereas cardiac autonomic dysfunction was impaired in the group with HbA1c ≥8.4%.
Natural Progression of Diabetic Peripheral Neuropathy in the Zenarestat Study Population
Authors: Brown Mark J. , Bird Shawn J. , Watling Sharon , Kaleta Hong , Hayes Lee , Eckert Stephen , Foyt Howard L.
Published: March 2007

OBJECTIVE—The aim of this study was to report the baseline and natural progression of diabetic peripheral neuropathy over 12 months in a large mild-to-moderate neuropathy population.

RESEARCH DESIGN AND METHODS—Patients from a multicentered trial of zenarestat, an aldose reductase inhibitor, had serial measures of neurologic function, including nerve conduction studies (NCSs), quantitative sensory testing (QST), and clinical neuropathy rating scores at baseline and at 12 months. Baseline population descriptors and changes in neurologic function in placebo-treated patients were analyzed.

RESULTS—Sural sensory velocity (P = 0.0008 [95% CI −1.04 to −0.27]), median sensory amplitude (P = 0.0021 [−1.3 to −0.29]), median distal motor latency (P = 0.002 [0.09–0.28]), cool thermal QST (P = 0.0005 [0.27–0.94]), and Michigan Neuropathy Screening Instrument results (P = 0.0087 [0.04–0.30]) declined significantly from baseline in the placebo population. NCS changes from baseline were independent of baseline HbA1c stratification.

CONCLUSIONS—The neurologic decline over 12 months is evident when measured by NCS and cool thermal QST. Other measures (vibration QST, neuropathy rating scores, monofilament examination) are insensitive to changes over 12 months in a mild-to-moderate affected population of this size.
Biological Variation in HbA1c Predicts Risk of Retinopathy and Nephropathy in Type 1 Diabetes
Authors: McCarter Robert J. , Hempe James M. , Gomez Ricardo , Chalew Stuart A.
Published: March 2007

OBJECTIVE—We hypothesized that biological variation in HbA1c, distinct from variation attributable to mean blood glucose (MBG), would predict risk for microvascular complications in the Diabetes Control and Complications Trial (DCCT).

RESEARCH DESIGN AND METHODS—A longitudinal multiple regression model was developed from MBG and HbA1c measured in the 1,441 DCCT participants at quarterly visits. A hemoglobin glycation index (HGI = observed HbA1c - predicted HbA1c) was calculated for each visit to assess biological variation based on the directional deviation of observed HbA1c from that predicted by MBG in the model. The population was subdivided by thirds into high-, moderate-, and low-HGI groups based on mean participant HGI during the study. Cox proportional hazard analysis compared risk for development or progression of retinopathy and nephropathy between HGI groups controlled for MBG, age, treatment group, strata, and duration of diabetes.

RESULTS—Likelihood ratio and t tests on HGI rejected the assumption that HbA1c levels were determined by MBG alone. At 7 years’ follow-up, patients in the high-HGI group (higher-than-predicted HbA1c) had three times greater risk of retinopathy (30 vs. 9%, P < 0.001) and six times greater risk of nephropathy (6 vs. 1%, P < 0.001) compared with the low-HGI group.

CONCLUSIONS—Between-individual biological variation in HbA1c, which is distinct from that attributable to MBG, was evident among type 1 diabetic patients in the DCCT and was a strong predictor of risk for diabetes complications. Identification of the processes responsible for biological variation in HbA1c could lead to novel therapies to augment treatments directed at lowering blood glucose levels and preventing diabetes complications.
Neuroendocrine Tumor Markers and Enterochromaffin-Like Cell Hyper/Dysplasia in Type 1 Diabetes
Authors: De Block Christophe E.M. , Colpin Gert , Thielemans Kristof , Coopmans Willy , Bogers Johannes J.P.M. , Pelckmans Paul A. , Van Marck Eric A.E. , Van Hoof Viviane , Martin Manou , De Leeuw Ivo H. , Bouillon Roger , Van Gaal Luc F.
Published: March 2007

OBJECTIVE—Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia.

RESEARCH DESIGN AND METHODS—Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA+ and 62 PCA−, aged 45 ± 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies.

RESULTS—PCA+ patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA− subjects. ECL cell hyper/dysplasia was present in seven PCA+ patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (β = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA+ patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor.

CONCLUSIONS—PCA+ patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.
Excess Hospitalizations, Hospital Days, and Inpatient Costs Among People With Diabetes in Andalusia, Spain
Authors: Olveira-Fuster Gabriel , Olvera-Márquez Pilar , Carral-Sanlaureano Florentino , González-Romero Stella , Aguilar-Diosdado Manuel , Soriguer-Escofet Federico
Published: March 2007

OBJECTIVE—The goal of this study was to estimate the excess hospitalizations, hospital days, and inpatient costs attributable to diabetes in Andalusia, Spain (37 hospitals, 7,236,459 inhabitants), during 1999 compared with those without diabetes.

RESEARCH DESIGN AND METHODS—This study was an analysis of all hospital discharges. Those with an ICD-9-CM code of 250 as either the main or secondary diagnosis were considered to have been admissions of individuals with diabetes. An estimate of costs was applied to each inpatient admission by assigning a cost weight based on the diagnostic-related group (DRG) related to each admission.

RESULTS—A total of 538,580 admissions generated 4,310,654 hospital bed-days and total costs of €940,026,949. People with diabetes accounted for 9.7% of all hospital discharges, 13.8% of total stays, and 14.1% of the total cost. Of the total cost for individuals with diabetes (€132,509,217), 58.3% were excess costs, of which 47% was attributable to cardiovascular complications and 43% to admissions for comorbid diseases. Individuals 45–75 years of age accounted for 75% of the excess costs. The rate of admissions during the study year was 145 per 1,000 inhabitants for individuals with diabetes compared with 70 admissions per 1,000 inhabitants for individuals without diabetes.

CONCLUSIONS—The costs arising from hospitalization of individuals with diabetes are disproportionate in relation to their prevalence. For those aged ≥45 years, cardiovascular complications were clearly the most important factor determining increased costs from diabetes.
Is Atherosclerosis in Diabetes and Impaired Fasting Glucose Driven by Elevated LDL Cholesterol or by Decreased HDL Cholesterol?
Authors: Drexel Heinz , Aczel Stefan , Marte Thomas , Benzer Werner , Langer Peter , Moll Willi , Saely Christoph H.
Published: March 2007

OBJECTIVE—To evaluate the atherogenicity of lipids in coronary patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes.

RESEARCH DESIGN AND METHODS—Serum lipid values, the presence of angiographic coronary artery disease (CAD) at baseline, and the incidence of vascular events over 2.3 years were recorded in 750 consecutive patients undergoing coronary angiography.

RESULTS—Triglycerides significantly (P < 0.001) increased and HDL cholesterol (P < 0.001) as well as LDL particle diameter (P < 0.001) significantly decreased from subjects with NFG <5.6 mmol/l (n = 272) over patients with IFG ≥5.6 mmol/l (n = 314) to patients with type 2 diabetes (n = 164). Factor analysis revealed two factors in the lipid profiles of our patients: triglycerides, HDL cholesterol, apolipoprotein A1, and LDL particle diameter loaded high on an HDL-related factor, and total cholesterol, LDL cholesterol, and apolipoprotein B loaded high on an LDL-related factor. In patients with type 2 diabetes, the HDL-related factor (odds ratio 0.648 [95% CI 0.464–0.904]; P = 0.011), but not the LDL-related factor (0.921 [0.677–1.251]; P = 0.597), was associated with significant coronary stenoses ≥50%. Consistently, in the prospective study, the HDL-related factor (0.708 [0.506–0.990]; P = 0.044), but not the LDL-related factor (1.362 [0.985–1.883]; P = 0.061), proved significantly predictive for vascular events in patients with type 2 diabetes.

CONCLUSIONS—The low HDL cholesterol/high triglyceride pattern is associated with the degree of hyperglycemia. In coronary patients with type 2 diabetes, this pattern correlates with the prevalence of CAD and significantly predicts the incidence of vascular events.