Factors associated with increased healthcare costs in Medicare Advantage patients with type 2 diabetes enrolled in a large representative health insurance plan in the US.

AIM: The objective of this study was to apply quantile regression (QR) methodology to a population from a large representative health insurance plan with known skewed healthcare utilization attributes, co-morbidities, and costs in order to identify predictors of increased healthcare costs. Further, this study provides comparison of the results to those obtained using ordinary least squares (OLS) regression methodology. METHODS: Members diagnosed with Type 2 Diabetes and with 24 months of continuous enrollment were included. Baseline patient demographic, clinical, consumer/behavioural, and cost characteristics were quantified. Quantile regression was used to model the relationship between the baseline characteristics and total healthcare costs during the follow-up 12 month period. RESULTS: The sample included 83,705 patients (mean age = 70.6 years, 48% male) residing primarily in the southern US (78.1%); 81.2% of subjects were on oral-only anti-diabetic therapy. Co-morbid conditions included nephropathy (43.5%), peripheral artery disease (26.4%), and retinopathy (18.0%). Variables with the strongest relationship with costs during the follow-up period included outpatient visits, ER visits, inpatient visits, and Diabetes Complications Severity Index score during the baseline period. In the top cost quantiles, each additional glycohemoglobin (HbA1c) test was associated with cost savings ($1400 in the 98th percentile). Stage 4 and Stage 5 chronic kidney disease were associated with an incremental cost increase of $33,131 and $106,975 relative to Stage 1 or no CKD in the 98th percentile ($US). CONCLUSIONS: These results demonstrate that QR provides additional insight compared to traditional OLS regression modeling, and may be more useful for informing resource allocation to patients most likely to benefit from interventions. This study highlights that the impact of clinical and demographic characteristics on the economic burden of the disease vary across the continuum of healthcare costs. Understanding factors that drive costs on an individual patient level provide important insights that will help in ameliorating the clinical, humanistic, and economic burden of diabetes.

Treatment patterns among older patients with type 2 diabetes in the United States: a retrospective cohort study.

BACKGROUND: The American Diabetes Association consensus statement on the treatment of type 2 diabetes mellitus (T2DM) in older patients highlights the need for treatment pattern and effectiveness data from real-world settings and populations. This retrospective cohort study assessed the relative frequency of use of four commonly prescribed antihyperglycemia treatments for T2DM and quantified their effectiveness up to 2 years post-initiation. SUBJECTS AND METHODS: Within a large, U.S.-based, electronic health record database, we investigated usage of insulin, sulfonylureas, glucagon-like peptide-1(GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with T2DM, focusing on those ≥65 years old, although younger patients were included for comparative purposes. RESULTS: Inclusion criteria were met by 77,440 patients. Mean baseline glycosylated hemoglobin (HbA1c) levels for patients ≥65 years old varied among treatments: insulin (7.7% [61 mmol/mol]; n=3,311), sulfonylureas (7.0% [53 mmol/mol]; n=5,706), GLP-1 receptor agonists (7.1% [54 mmol/mol]; n=260), and DPP-4 inhibitors (7.1% [54 mmol/mol]; n=1,096). Older patients demonstrated good glycemic control at therapy initiation and were prescribed glucose-lowering agents at lower HbA1c values compared with younger patients. A large proportion of older patients were prescribed sulfonylureas (56%) and insulin (34%) compared with GLP-1 receptor agonists (3.4%) and DPP-4 inhibitors (12%), despite the associated risk of hypoglycemia. CONCLUSIONS: Patients initiating insulin and sulfonylureas demonstrated more sustained glycemic control compared with GLP-1 receptor agonists and DPP-4 inhibitors. A majority of older patients with T2DM was initiated on sulfonylureas and insulin at relatively low levels of HbA1c, a practice not entirely consistent with the recommendations of published guidelines.

The effect of PPI use on human gut microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) achieves sustainable weight loss possibly by altering the gut microbiota. The effect of a proton pump inhibitor (PPI) on weight loss and the gut microbiota has not been explored. PPI use and the gut microbiota were assessed before and 6 months after LRYGB in eight patients. Bacterial profiles were generated by 16S ribosomal RNA (rRNA) gene sequencing. Prior to LRYGB, PPI users had a higher percent relative abundance (PRA) of Firmicutes compared to nonusers. PPI users at 6 months post-LRYGB had a higher PRA of Firmicutes [48.6 versus 35.6%, p = nonsignificant (NS)] and a trend toward significantly lower percent excess weight loss (49.3 versus 61.4%, p = 0.067) compared to nonusers. PPI use post-LRYGB may impair weight loss by modifying gut microbiota.

Frequency and causes of hospitalization in older compared to younger adults with type 2 diabetes in the United States: a retrospective, claims-based analysis.

AIMS: This study assessed the frequency and most common causes of hospitalization in older compared to younger adults with type 2 diabetes mellitus (T2DM) in the US. METHODS: A retrospective study utilizing data from a nationally representative insurance claim database included patients who were diagnosed or treated for diabetes during or prior to the defined study period and who experienced hospitalization with or without re-hospitalization. RESULTS: Among 887,182 patients with T2DM, 31% were ≥ 65 years old and nearly 1 in 4 (23.5%) were hospitalized during the observation period. Only 2.3% of first hospitalizations were determined to be diabetes-related, and these events were most commonly associated with a history of pre-study hospitalization and increasing age. Hypoglycemia was a common cause for T2DM-related hospitalizations (22.9%), and older patients demonstrated a higher proportion of hypoglycemia-related hospitalizations (age ≥ 65 years: 38.3% vs. age < 65 years: 11.4%). Survival analysis predicting readmission within 6 months after first hospitalization showed that primary factors associated with first readmissions were history of prior hospitalization, malignancy, insulin use, and presence of pre-existing liver or renal disease. CONCLUSIONS: Hospitalization is common in patients with diagnosed diabetes, and nearly 1 in 4 diabetes-related hospital admissions were due to hypoglycemia. While the overall rate of hypoglycemia-associated admission was low, the age-specific rate was nearly 2.5-fold higher in older adults (≥ 65 years), affirming the need to carefully assess the potential benefit/risk of diabetes medications in those ≥ 65 years of age.

Regional and overall aortic function in nondiabetic individuals with insulin resistance and normal glucose tolerance.

CONTEXT: Insulin resistance is associated with altered vascular function in diabetes. OBJECTIVE: The objective of the study was to define the overall and regional aortic function as well as the changes of aortic function over time in nondiabetic individuals with insulin resistance and a normal oral glucose tolerance test (OGTT). DESIGN: This was a cross-sectional and longitudinal analysis with 12 months follow-up. SETTING: The setting of the study was in primary care. PATIENTS: Nondiabetic individuals (n = 181, mean age 42 ± 8 y) with a normal OGTT and insulin resistance as defined by the insulin sensitivity index (ISI) participated in the study. INTERVENTIONS: ISI was estimated from serial measurements of plasma insulin and glucose during an iv glucose tolerance test. Ascending and abdominal aortic distensibility (AoD) and stiffness index-ß (AoSI) were assessed using echocardiography. Carotid-to-femoral artery pulse wave velocity (PWVc-f; an index of overall aortic function) was measured from carotid and femoral arteries Doppler flow velocities recorded simultaneously with an electrocardiogram. Associations between ISI, AoD, AoSI, and PWVc-f were assessed using linear regression analyses and ANOVA. Differences between baseline and 12 months were compared using a paired t test. MAIN OUTCOME MEASURES: AoD and AoSI associations as well as changes over a 12-month period in relation to ISI were measured. RESULTS: Ascending AoD (P = .01) and ascending AoSI (P = .025) were significantly associated with ISI; in contrast, abdominal AoD and AoSI and PWVc-f did not. Changes in AoD, AoSI, and PWVc-f over time were more prominent in individuals with low ISI compared with those with high ISI. CONCLUSIONS: The significant associations between ISI and aortic function suggest that insulin resistance may affect the cardiovascular system, even when OGTT is normal.

Cardiovascular recovery following bariatric surgery in extremely obese adolescents: preliminary results using Cardiac Magnetic Resonance (CMR) Imaging.

PURPOSE: Baseline cardiovascular characteristics and longitudinal changes following weight loss surgery (WLS) in adolescents are not well defined. Recent data suggest that the use of transthoracic echocardiography (TTE) for preoperative cardiac assessment may provide suboptimal imaging fidelity secondary to excessive upper body adiposity. High fidelity imaging using cardiac magnetic resonance (CMR) is an extremely useful diagnostic tool. We report the use of CMR in a cohort of extremely obese adolescents undergoing WLS. METHODS: A retrospective analysis of adolescent WLS patients at a single institution was conducted. Data collection included mean age, sex, body mass index (BMI), and CMR measurements of left ventricular (LV) mass, LV end-diastolic volume (LVEDV), ejection fraction (EF), and myocardial perfusion reserve index (MPRI). Comparison of CMR results to normative data derived from lean subjects was performed. RESULTS: Ten subjects (9 female), with a mean age and BMI of 17.4 ± 1.9 years and 50.33 ± 10.21 kg/m(2) respectively, were studied. When compared to age, gender, and height matched normal weight (NW) controls, the obese (OB) subjects had evidence of increased LV mass (122 ± 25 g vs. 101 ± 10 g, OB vs. NW respectively, p<0.05), and increased LVEDV (156 ± 25 mL vs. 109 ± 9 mL, p<0.05), with an average EF of 61.5% ± 5% (range 52% to 67% vs. 71% to 74% expected EF for males and females, respectively, p=0.003). In addition, 60% of the OB subjects (6/10) demonstrated adenosine-induced sub-endocardial ischemia at baseline, the majority of whom underwent WLS (n=5) resulting in complete normalization of ischemia in 60% (3/5) and partial improvement in 40% (2/5). A reduction in mean LV mass (range 2 to 12 g) following WLS was observed. CONCLUSION: Extreme adolescent obesity is associated with significant cardiovascular abnormalities that include LV hypertrophy (i.e. increased LV mass) and LV dilatation. These findings, considered to be well-recognized cardiovascular disease risk factors in adults, were shown to be reversible after WLS in the small group of subjects studied here. Additional large-scale investigations designed to examine obesity-related cardiovascular disease in severely obese adolescents are required.

Relationship between glycemic control and readmission rates in patients hospitalized with congestive heart failure during implementation of hospital-wide initiatives.

OBJECTIVE: To determine the relationship between inpatient glycemic control and hospital readmission in patients with congestive heart failure (CHF). METHODS: We used an electronic data collection tool to identify patients with a discharge diagnosis of CHF who underwent point-of-care glucose assessments. Timeweighted mean glucose (TWMG), hemoglobin A1c, and glycemic lability index (GLI) served as glycemic indicators, and readmission for CHF was determined at 30 days and between 30 and 90 days. RESULTS: The analysis included 748 patients. After adjustment for significant covariates, log-transformed increasing TWMG (odds ratio 3.3; P = .03) and log-transformed hemoglobin A1c (odds ratio 5.5; P = .04) were independently associated with higher readmission for CHF between 30 and 90 days, but not by 30 days. Renal disease, African American race, and year of hospital admission were also significantly associated with readmission, but GLI was not. There was no significant difference in TWMG when analyzed on the basis of race or renal status. We noted a decrease in TWMG (P = .004) and a trend for reduction in readmission rates between 30 and 90 days (P = .06) after hospital-wide interventions were implemented to improve glycemic control, but no significant difference was detected in GLI or hypoglycemia. CONCLUSION: Increasing glucose exposure, but not glycemic variability, was associated with higher risk of readmission between 30 and 90 days in patients with CHF. Prospective studies are needed to confirm or refute these results.

Obesity and the development of type 2 diabetes: the effects of fatty tissue inflammation.

Obesity is a worldwide epidemic with multiple obesity-associated health problems including type 2 diabetes, hypertension, and cardiovascular disease. Adipose tissue serves as a fuel storage depot, but also plays a pivotal role in homeostasis of energy expenditure, appetite regulation, glucose regulation, and immunity. Both genetics and environment play important roles in adipose tissue function and dysfunction. Obesity represents an abnormal accumulation of adipose tissue resulting from chronic overnutrition and reduced physical activity. The nature of this increased accumulation of fat tissue, whether hyperplasia or hypertrophy, local or ectopic, is associated with deleterious perturbations including excess fatty acid secretion, increased production of inflammatory cytokines, and abnormal adipocyte hormone signaling resulting in insulin resistance. In the setting of obesity, insulin resistance and chronic inflammation is postulated to play a role in development of type 2 diabetes and other obesity-related comorbidities including obstructive sleep apnea, hepatic steatosis, polycystic ovarian syndrome, hypertension and cardiovascular disease. Although the exact mechanism of these relationships are complex and not completely understood, the ability to store and limit fatty acid deposition to adipose tissue is a common component to remaining insulin sensitive, controlling the inflammatory cascade and reducing the risk of developing obesity-related comorbidities.

Childhood obesity: a risk factor for injuries observed at a level-1 trauma center.

PURPOSE: Obesity is an independent risk factor in trauma-related morbidity in adults. The purpose of this study was to investigate the effect of obesity in the pediatric trauma population. METHODS: All patients (6-20 years) between January 2004 and July 2007 were retrospectively reviewed and defined as non-obese (body mass index [BMI] <95th percentile for age) or obese (BMI > or =95th percentile for age). Groups were compared for differences in demographics, initial vital signs, mechanisms of injury, length of stay, intensive care unit stay, ventilator days, Injury Severity Score, operative procedures, and clinical outcomes. RESULTS: Of 1314 patients analyzed, there were 1020 (77%) nonobese patients (mean BMI = 18.8 kg/m(2)) and 294 (23%) obese patients (mean BMI = 29.7 kg/m(2)). There was no significant difference in sex, heart rate, length of stay, intensive care unit days, ventilator days, Injury Severity Score, and mortality between the groups. The obese children were significantly younger than the nonobese children (10.9 +/- 3.3 vs 11.5 +/- 3.5 years; P = .008) and had a higher systolic blood pressure during initial evaluation (128 +/- 17 vs 124 +/- 16 mm Hg, P < .001). In addition, the obese group had a higher incidence of extremity fractures (55% vs 40%; P < .001) and orthopedic surgical intervention (42% vs 30%; P < .001) but a lower incidence of closed head injury (12% vs 18%; P = .013) and intraabdominal injuries (6% vs 11%; P = .023). Evaluation of complications showed a higher incidence of decubitus ulcers (P = .043) and deep vein thrombosis (P = .008) in the obese group. CONCLUSION: In pediatric trauma patients, obesity may be a risk factor for sustaining an extremity fracture requiring operative intervention and having a higher risk for certain complications (ie, deep venous thrombosis [DVT] and decubitus ulcers) despite having a lower incidence of intracranial and intraabdominal injuries. Results are similar to reports examining the effect(s) of obesity on the adult population.

Changes in physiology with increasing fat mass.

Obesity has reached epidemic proportions in the USA with a nearly fourfold rise in the prevalence of childhood obesity. There are many possible etiologies of obesity as the adipose tissue plays a significant, complex role in the physiology of fuel metabolism and hormone regulation. The development of obesity represents a pathophysiologic increase in fat mass in which multiple metabolic pathways are deranged. The consequences of these metabolic derangements, including insulin resistance and inflammation, are reflected in obesity-related comorbidities and can be seen in the setting of pediatric obesity. Obese adolescents demonstrate increased rates of early maturation, orthopedic growth abnormalities, diabetes mellitus, obstructive sleep apnea, hypertension, steatosis, and polycystic ovarian syndrome, placing this group of children at risk for long-term health problems and reduced quality of life. Given the negative short- and long-term impact of obesity on children, careful attention should be paid to the unique health issues of this "at-risk" population with both prevention and early intervention strategies.

Resistance training differentially affects weight loss and glucose metabolism of White and African American patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to identify whether racial differences in body composition and glucose metabolism occur in response to exercise and determine whether aerobic and resistance exercise modalities bring about differential changes in these parameters in African Americans and White persons with type 2 diabetes. RESEARCH DESIGN AND METHODS: Participants included 36 African American and 23 White men and women with type 2 diabetes who were randomly assigned to eight weeks of either resistance or aerobic exercise. Before and after this intervention, each participant underwent a series of measurements that assessed anthropometrics and glucose metabolism. RESULTS: African Americans responded more favorably to resistance training than did Whites. This difference was manifested by a significant improvement in BMI (-2.57%+/-.90% vs 2.57%+/-1.09%, P<.01) and insulin resistance (-19.15%+/-9.00% vs 13.12%+/-11.86%, P<.05) in African Americans compared to Whites. When comparing exercise modalities within the races, African Americans demonstrated a preferential response to resistance training. CONCLUSIONS: Eight weeks of resistance training by African Americans may have a more positive effect on weight loss and glucose metabolism than aerobic exercise training. Furthermore, the changes observed appear to be unique to African Americans, as no changes were observed in Whites after an equal amount of resistance training. When an exercise program is designed for a person with type 2 diabetes, race should be taken into consideration, and resistance exercise for African Americans may lead to increased weight loss and improved insulin sensitivity than does aerobic exercise.

Short-term aerobic exercise training in obese humans with type 2 diabetes mellitus improves whole-body insulin sensitivity through gains in peripheral, not hepatic insulin sensitivity.

CONTEXT: Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus; however, the contributions of peripheral and hepatic tissues to these improvements are not known. OBJECTIVE: Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions. DESIGN: Subjects were randomly assigned to one of two groups. The energy balance group consumed an isocaloric diet consisting of 50% carbohydrate, 30% fat, and 20% protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70% of maximum oxygen consumption maximum during the second 7 d of the 15-d study period. Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study. SETTING: The study was performed at Ohio State University's General Clinical Research Center. PARTICIPANTS: There were 18 obese, mildly diabetic humans included in the study. INTERVENTION: Aerobic exercise training was performed for 7 d. MAIN OUTCOME MEASURES: Whole-body, peripheral, and hepatic insulin sensitivity were measured. RESULTS: Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin. Likewise, it did not alter endogenous glucose production during high-dose insulin. However, 1-wk of exercise training increased both whole-body (P<0.05) and peripheral insulin sensitivity (P<0.0001) during high-dose insulin. CONCLUSION: Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral, not heptic insulin sensitivity.

The cardiometabolic syndrome in persons of the African diaspora: challenges and opportunities.

Unique genetic traits appear to play a role in the increased rates of hypertension (HTN), glucose dysregulation/diabetes (T2DM), and obesity in persons of African descent. Indeed, with increasing rates of westernization/urbanization and concomitant increases in obesity and T2DM, a similar predisposition to the cardiometabolic syndrome and cardiovascular disease (CVD) can be seen in Africans compared with persons of African descent, with CVD reaching epidemic proportions in many areas of Africa. In addition, the complex relationships of metabolic abnormalities that are unique to individuals of African descent have also been demonstrated in Africans. These include: (1) a dissociation of HTN to insulin resistance; (2) relative favorable lipid profile in the setting of increasing rates of CVD; (3) low levels of visceral adiposity in the setting of obesity and insulin resistance; and (4) a dissociation of insulin sensitivity and adiponectin when compared with Caucasians. Although not well understood, these unique relationships suggest that conventional parameters for CVD do not apply to Africans of persons of African descent.

Association between glycosylated hemoglobin, left ventricular mass and aortic function in nondiabetic individuals with insulin resistance.

OBJECTIVE: An association between glycosylated hemoglobin (GHb) and cardiovascular mortality in nondiabetic individuals has recently been reported. Prompt detection of nondiabetic individuals with high-normal GHb and early cardiovascular involvement may be of value for preventive strategies. In this investigation, a possible relationship between GHb, aortic function and left ventricular (LV) mass in nondiabetic individuals has been studied. METHODS: A total of 263 nondiabetic African-Americans, aged 22-63 (mean 42 +/- 8) years were studied. All individuals were first degree relatives of diabetic patients, had normal oral glucose tolerance test (2-h OGTT) and decreased peripheral action of insulin. LV diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, arterial pressure); pulse wave velocity (PWV; electrocardiography, Doppler); fasting glucose; GHb; insulin sensitivity index (S(I)) and 2-h OGTT were measured. Multiple linear and logistic regression analyses were used to identify significant independent associations of fasting glucose; GHb; S(I) and 2-h OGTT with aortic function and LV mass. RESULTS: In fully adjusted multivariate logistic regression analysis, GHb predicted lower values of aortic distensibility (odds ratio (OR) 1.67 95% CI (1.04-2.75), P=0.04); higher PWV (OR 1.79 95% CI (1.09-2.93), P=0.022); and higher values of LV mass (OR 1.56 95% CI (1.08-2.88), P=0.029). Fasting glucose, S(I), and 2 h OGTT were not associated with aortic function and LV mass. CONCLUSION: Higher GHb concentrations, even within 'normal' range, are independently associated with stiffer aorta and increased LV mass and thus may detect nondiabetic individuals at increased cardiovascular risk.

Cardiovascular effects of type 1 diabetes mellitus in children.

Previous studies have shown that type 1 diabetes mellitus (DM) is associated with cardiovascular abnormalities. Early detection and treatment of these abnormalities may help to prevent the natural progression of the disease. The present study was undertaken to define early cardiovascular abnormalities in children with type 1 DM. Simultaneous evaluation of multiple cardiovascular parameters was performed in 14 children with type 1 DM and 14 age-and gender-matched normal subjects. Measurements of carotid artery intima-media thickness (cIMT, echocardiography), carotid and aortic (ascending and abdominal) distensibility (echocardiography, brachial artery blood pressure), aortic pulse wave velocity (carotid to femoral artery, Doppler), and left ventricular dimensions, mass, and function (echocardiography) were performed. Diabetic children demonstrated a greater cIMT (0.36 +/- 0.04 mm vs 0.31 +/- 0.03 mm, p = 0.002) and decreased carotid artery distensibility (4.4 +/- 1.6 cm(2) . dynes(-1) . 10(-6) vs 6.0 +/- 1.9 cm(2) . dynes(-1) .10(-6), p < 0.01) compared to control. Aortic pulse wave velocity was increased in DM (6.70 +/- 0.39 vs 6.30 +/- 0.31, p = 0.02) compared to control. Left ventricular diameters, mass, and systolic and diastolic function did not differ between the 2 groups. Simultaneous assessment of multiple cardiovascular parameters in children with type 1 DM revealed impaired carotid artery structure and function, and decreased elastic properties of the aorta, before demonstrable changes in left ventricular structure and function could be detected.

Long-term cardiovascular effects of insulin sensitizer troglitazone on non-diabetic individuals with insulin resistance: double blind, prospective randomized study.

OBJECTIVES: The study was undertaken to assess the long-term cardiovascular effects of troglitazone on non-diabetic individuals with insulin resistance. BACKGROUND: It has been suggested that treatment with troglitazone or similar insulin-sensitizing agents may prevent cardiovascular complications in non-diabetic individuals with insulin resistance. However, the long-term cardiovascular effects of these agents on non-diabetic individuals remain to be defined. METHODS: A total of 137 African-American offspring of type 2 diabetic parents, with normal glucose tolerance and insulin resistance, were randomly divided to receive troglitazone 200 mg/day (n = 40), or placebo (n = 97) for 24 months. Brachial artery blood pressure (sphygmomanometry); aortic pulse wave velocity (carotid to femoral artery, Doppler), left ventricular diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, blood pressure); and metabolic and lipid profile were assessed at baseline, 12, and 24 months after randomization (delta 12, delta 24 respectively). RESULTS: The pulse wave velocity increased significantly in the troglitazone group compared to placebo group (p < 0.05). Changes from baseline in the troglitazone group were significant (delta 12 = 1.09 +/- 0.36 m/sec, delta 24 = 2.08 +/- 0.45 m/sec, ANOVA p < 0.001), while pulse wave velocity remained unchanged in the placebo group. This increase in pulse wave velocity is consistent with a decrease in the elastic properties of the aorta. CONCLUSIONS: Long-term administration of troglitazone to non-diabetic African-Americans with insulin resistance was associated with a decrease in the elastic properties of the aorta. Long-term therapy with troglitazone or similar agents for the prevention of cardiovascular complications in non-diabetic individuals with insulin resistance has to be critically evaluated.

Diabetes in Africa. Pathogenesis of type 1 and type 2 diabetes mellitus in sub-Saharan Africa: implications for transitional populations.

The increasing prevalence and incidence of diabetes and its long-term complications in sub-Saharan Africa (SSA) could have devastating human and economic toll if the trends remain unabated in the future. Approximately 90% or majority of patients with diabetes belongs to the adult onset, type 2 diabetes category while 10% have type 1 diabetes in SSA. However, because of the paucity of metabolic and clinical data, a clear understanding of the natural history of both diseases and the classification of diabetes subtypes has been hampered. Nevertheless, we have attempted to provide a concise review of the pathophysiology of both type 1 and type 2 diabetes as well as phenotypic and clinical variations in patients residing in SSA. The limited metabolic data, (albeit increasing), from high-risk and diabetic individuals in the SSA, have contributed significantly to the understanding of the pathogenetic mechanisms of diabetes and the variations in the presentation of the disease. Sub-Saharan African patients with type 1 diabetes have essentially absolute insulin deficiency. In addition, patients with type 2 diabetes in SSA region also manifest severe insulin deficiency with varying degrees of insulin resistance. Although the exact genetic markers of both diseases are unknown, we believe studies in patients of SSA origin who reside in diverse geographic environments (African diaspora) could potentially contribute to our understanding of the genetic and environmental mediators of both diseases. However, many intrinsic, individual and societal obstacles such as poor education and illiteracy, low socio-economic status and lack of access to health care make uncertain the translation of diabetes research in SSA. In this regard, effective management and/or prevention of diabetes in SSA individuals should adopt multidisciplinary approaches. Finally, innovative health care delivery and educational models will be needed to manage diabetes and its long-term complications in SSA.

Insulin resistance, beta cell function and cardiovascular risk factors in Ghanaians with varying degrees of glucose tolerance.

OBJECTIVE: Type 2 diabetes is characterized by beta cell dysfunction and insulin resistance (IR). The disease is associated with high rates of cardiovascular mortality and morbidity. Recently, the American Diabetes Association Expert Committee recommended the measurement of fasting glucose as a tool for screening and diagnosing diabetes, in order to identify patients with a mild form of the disease as well as to enhance the detection of undiagnosed type 2 diabetes. The significance of these criteria with respect to cardiovascular risk factors in native Ghanaians is unknown. The objectives of the present study were to examine the cardiovascular risk factors in a sample of native Ghanaians with varying degrees of glucose intolerance as defined by fasting glucose levels as specified by the ADA criteria. RESEARCH AND METHODS: The population consisted of 200 indigenous Ghanaian subjects, age range 25-74 years, residing in the Accra metropolitan areas. Subjects were categorized using the fasting plasma glucose (FPG) alone as normal fasting glucose (NFG, FPG < 110 mg/ dL), impaired fasting glucose (IFG, 11 < FPG 126 mg/dL), and diabetic (DM, FPG > 126 mg/ dL). Anthropometric parameters (blood pressure, waist circumference and waist-hip circumference ratios) were measured in each subject. Levels of serum glucose, c-peptides and insulin were measured at baseline and after 2 hours of oral glucose challenge. Insulin resistance (HOMA-IR) and beta cell function (HOMA-%B) were assessed by homeostasis model assessment (HOMA). Levels of fasting serum cholesterol, high-density lipoprotein cholesterol (HDL-C), cholesterol, and triglycerides were measured in each subject. RESULTS: There were 181 subjects in the NFG category, 11 in the IFG category, and 8 newly diagnosed type 2 diabetic subjects. The mean age, BMI, waist circumference (WC), and WHR did not differ between the 3 groups. The mean fasting glucose and the corresponding 2-hour glucose levels rose with the worsening of glucose tolerance. Similarly, the means for serum fasting, post-challenge serum insulin, and c-peptide levels were significantly greater in the IFG and DM groups. Fasting serum cholesterol and high density lipoproteins did not differ statistically between the 3 groups, However, the means for serum triglycerides were greater in the IFG and DM groups when compared to the NFG group. The insulin resistance (IR) as assessed by HOMA was 2x and 4x greater in the IFG (3.76) and DM (6.12) groups when compared with the NFG (1.82, P < .05). CONCLUSIONS: We have characterized the metabolic and anthropometric risk factors for CVD in native Ghanaians with varying degrees of glucose tolerance, as defined by the ADA criteria. We found that both IFG and DM were associated with beta cell dysfunction, insulin resistance, and elevated serum triglycerides. However, the well established cardiovascular risk factors, such as body mass index, body fat distribution, and blood pressure did not track with the increasing glucose intolerance in the native Ghanaians. We conclude that the Ghanaian patients with IFG and type 2 diabetes were non-obese and exhibited severe beta cell dysfunction, insulin resistance, and elevated triglycerides, but none of the other conventional risk factors, at the time of diagnosis. Future research should focus on the sequential changes in risk factors during development of cardiovascular diseases in native Ghanaians with varying degrees of glucose tolerance.

Pathogenic mechanism of type 2 diabetes in Ghanaians--the importance of beta cell secretion, insulin sensitivity and glucose effectiveness.

OBJECTIVE: To assess insulin sensitivity and beta cell secretion in indigenous Ghanaian subjects with a spectrum of glucose intolerance. RESEARCH AND METHODS: We evaluated beta cell secretion, insulin sensitivity (Si) and glucose effectiveness (Sg) in three groups: group 1, 15 healthy control subjects without family history of type 2 diabetes; group 2, 11 healthy non-diabetic first-degree relatives of Ghanaian patients with type 2 diabetes; and group 3, 10 patients with type 2 diabetes living in Accra, Ghana, West Africa. A standard oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance (FSIGT) test were performed for each subject. Si and Sg were measured using Bergman's minimal model method. RESULTS: The mean body mass index (BMI) and lean body mass were not different among the three groups. However, the waist-to-hip circumference ratio, total body fat as well as triceps and biceps skinfolds were significantly greater in group 3 (diabetic patients) than in group 2 (relatives) and group 1 (healthy controls). Mean fasting and postprandial serum glucose levels were not significantly different between the relatives and healthy controls during oral glucose challenge. The mean fasting and postprandial serum glucose levels were significantly higher in the group 3 diabetic patients than in the non-diabetic groups. Mean fasting serum insulin and C-peptide levels tended to be higher in group 3 than in groups 1 and 2. However, mean serum insulin and C-peptide responses after oral glucose load were significantly greater in group 2 than in the group 1 healthy controls. The insulin responses in the two non-diabetic groups after oral glucose challenge were significantly greater than in the diabetic patients. During the FSIGT, the mean serum glucose responses were similar in the two non-diabetic groups (groups 1 and 2). The serum glucose responses were significantly greater in group 3 than in the non-diabetic groups. Mean total and acute first and second phases of insulin and C-peptide responses were greater in group 2 than group 1. However, acute phases of insulin secretion were severely blunted in group 3 when compared with groups 1 and 2 during FSIGT in our Ghanaians. We found that the mean Si was slightly lower in group 2 (1.72 +/- 0.32) than in the healthy controls in group 1 (1.9 +/- 0.55, P = NS). Mean Si was remarkably lower in the diabetic patients in group 3 (1.30 +/- 0.35 x 10(-4)/min (microU/ml)) when compared with the relatives and healthy controls, but the differences were not statistically significant. Mean glucose effectiveness at basal insulin level (Sg) was not significantly different among the relatives in group 2 (2.38 +/- 0.50), the healthy controls in group 1 (2.66 +/- 0.38) and the diabetic patients in group 3 (2.27 +/- 0.49 x 10(-2)/min). CONCLUSIONS: We conclude that (i) the pathogenetic mechanisms of type 2 diabetes in indigenous Ghanaians are characterised by severe beta cell dysfunction and moderate reduction in Si. Although the healthy relatives manifest insulin resistance with compensatory hyperinsulinaemia, our study suggests that the conversion of such subjects to type 2 diabetes is determined by deterioration in beta cell function and perhaps Si but not tissue Sg in Ghanaians. Prospective studies are needed to examine the sequential changes that lead to the development of type 2 diabetes in indigenous Ghanaians.

Diabetes mellitus.

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes mellitus is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. The management of this disease process is complicated. Good diabetic control depends on diligence in blood glucose monitoring, frequent adjustment of medications, adherence to a regular diet and exercise plan, and treatment of comorbid conditions such as hypertension and hyperlipidemia.