Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus (Diabetes Metab J 2022;46:93-103)

See the letter "Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus" in Volume 46 on page 93.

Long-term influence of type 2 diabetes and metabolic syndrome on all-cause and cardiovascular death, and microvascular and macrovascular complications in Chinese adults — A 30-year follow-up of the Da Qing diabetes study

The association of type 2 diabetes mellitus and hypertension is so high that it cannot be explained on the basis of diabetic nephropathy. This phenomenon has been attributed to a condition known as metabolic syndrome. Depression may be another aspect of metabolic syndrome. We conducted a cross-control study with 110 patients with type 2 diabetes mellitus (DM) and 110 control subjects of comparable age and sex. We determined the time since diagnosis of diabetes, the presence of hypertension (HT), coronary heart disease, cerebrovascular insufficiency, and depression, and took several anthropometric measurements, including height, weight, body mass index (BMI) waist circumference (WC), waist-to-hip circumference ratio (WHR), triceps skin fold thickness (TSFT), mid-upper arm circumference (MUAC), and mid-upper arm muscle area (MAMA). We also investigated depression in metabolic syndrome by comparing patients with type 2 diabetes alone and with type 2 diabetes and hypertension who attended a diabetes clinic. The prevalence of depression in hypertensive diabetics was 57% whereas in diabetics alone it was 40% (X2=4.3, P is less than 0.05). Likewise, combined hypertension and depression was more common among diabetics than controls (66% vs 25% respectively P is less than 0.01). The presence of combined hypertension and type 2 diabetes should alert the clinician to look for other features of the metabolic syndrome and for associated depression, which should be treated in most cases by pharmacotherapy.

Diabetes mellitus (DM) long-term macrovascular and microvascular complications pose significant health risks and increase mortality. In DM patients, metabolic syndrome (MetSy) either precedes or coexists with the condition. Central obesity, poor glycemic control, hypertension, elevated triglycerides (TG), and low high-density lipoproteins (HDL-C) are the components of MetSy. The purpose of this study is to investigate related diabetic microvascular complications in type 1 DM (T1DM) by comparing them with type 2 DM (T2DM), determine potential risk factors, and estimate prevalence based on the diagnosis of MetSy. This study included 160 T1DM and 160 T2DM patients, totaling 320 DM patients. It was carried out from April 20, 2022, to September 31, 2023, at the Sheikh Zayed Hospital, Rahim Yar Khan, in the Outdoor Diabetic Clinic and Medicine Department. A unique questionnaire was utilized to gather socio-demographic, general, clinical, and laboratory data for the MetSy criteria set forth by the International Diabetes Federation (IDF). The blood pressure, BMI, and waist circumference (WC) were measured, while venous fasting blood was used to assess biochemical markers such as HDL-C, TG, and fasting blood sugar. The microvascular diabetes complications were identified using abdominal ultrasound, fundus ophthalmoscopy, and routine laboratory tests.We quantified and analyzed these variables individually for T1DM and T2DM patients with or without MetSy and compared them in the presence or absence of diabetes microvascular complications. MetSy prevalence was 25.62% (41, n=160) for T1DM and 60.62% (97, n=160) for T2DM, totaling 43.12%. Among T1DM patients with MetSy, the majority were married males, aged 36-49 years, with a BMI of 26.69±2.20 kg/m2 and a WC of 85.12±4.23, and 67.5% (108) patients had diabetes microvascular complications. Comparatively, in T2DM with MetSy, the majority were married females aged 50-59 years with a BMI of 29.79 ± 4.65 kg/m² and a large WC of 93.43±4.49, and 75% (123) patients had diabetes microvascular complications. Overall, this study noted significant p-values for hypertension, elevated TG, low HDL-c, high WC, obesity, female gender in T2DM, and above 36 years of age in both groups with MetSy. Diabetic retinopathy (DR) at 32.4% (p<0.001) was the most prevalent T1DM microvascular complication, followed by nephropathy (30.6%), neuropathy (DN) at 28.1%, and gastroparesis (DG) at 22.3%. Whereas in T2DM, the prevalence of DN was 36.3% (p<0.001), followed by DKD (29.3%), DG (28.9%), and DR (24.9%). Nearly a quarter of T1DM patients had MetSy, with increasing percentages of overweight and obese patients who are more likely to have DR, DKD, or DN. MetSy affects two-thirds of T2DM patients, with married obese females aged 50-59 being more susceptible than males, who are more likely to suffer DN, DKD, or DG. Risk factors that contribute to the MetSy burden in T1DM and T2DM include hypertension, poor glycemic management, low HDL-C, high TG, and a higher BMI or WC. Increasing age, female gender in T2DM, longer diabetes duration, and co-morbid hypertension were independent predictors of microvascular complications. DR, DN, DKD, and gastroparesis are the most prevalent diabetic microvascular sequelae. The clinical management of diabetic patients with healthy lifestyle adaptations, good glycemic control, antihypertensives, and statins will contribute greatly to MetSy prevention.

BackgroundThe Metabolic syndrome (MS) consists of central obesity, glucose intolerance, hyperinsulinemia, low high density lipoproteins, high triglycerides and hypertension. Different studies have observed that MS causes microvascular complications in patients with type 2 diabetes. The aim of the study was to find out the prevalence of MS in the Indian population with type 2 diabetes mellitus in relation to gender, duration of diabetes, and to evaluate the influence of MS and its individual components on microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.MethodsA population-based cross sectional survey was conducted with 1414 patients having type 2 diabetes mellitus. The International Diabetes Federation (IDF) criteria were used to identify the metabolic syndrome. Diabetic retinopathy was graded using the stereoscopic digital fundus photography. Neuropathy was assessed by measuring the vibration perception threshold through a sensitometer. Nephropathy was diagnosed by the presence of microalbuminuria in the first morning urine sample.ResultsThe age and gender adjusted prevalence of MS, using the IDF criteria, in the South Indian population was 73.3%. The prevalence was higher in women (83.3%), compared to men (65.3%). In subjects with diabetes mellitus, without and with MS, the prevalence of retinopathy was 21.3% and 16.9% (p = 0.057); prevalence of nephropathy was 20.5% and 18.0% (p = 0.296), and prevalence of neuropathy was17.2% and 19.4% (p = 0.353) respectively. Overall and in women, the clustering of MS components led to an increase in the prevalence of diabetic nephropathy. The prevalence of retinopathy and neuropathy in MS subjects, who had diabetes for < 10 years, was more in both men and women; it was more in women but not in men when the duration of diabetes varied from 11-20 years.ConclusionsThe association of MS with microangiopathies decreased with an increase in the duration of diabetes. MS behaved differently in men and women. It may need to be managed differently in the two groups.

BackgroundBoth type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications.MethodsWe included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR).ResultsAmong the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P<0.05).ConclusionAlthough the prevalence of MetS in adult patients with T1DM in China was relatively low, patients with MetS were more likely to have DKD and DR. A comprehensive management including lifestyle modification might reduce their risk of microvascular complications in adults with T1DM.

BackgroundThe chronic macro and microvascular complications of diabetes mellitus pose serious health challenges. Metabolic syndrome (MetSy) is characterized by central obesity, glucose intolerance, hyperinsulinemia, low high-density lipoproteins (HDLs), high triglycerides (TGs), and hypertension. MetSy precedes or accompanies diabetes, and it has been linked to an increased risk of cardiovascular disease and premature death. This study aimed to estimate prevalence, identify risk factors, and evaluate associated microvascular complications among MetSy patients with type 2 diabetes mellitus (T2DM).MethodologyOver the period of March 20, 2022, to March 31, 2023, a prospective cohort study was conducted at the Outdoor Clinic and Medicine Department of Sheikh Zayed Hospital, Rahim Yar Khan. Based on the International Diabetes Federation MetSy criteria, a total of 160 patients fulfilling the inclusion criteria were selected.A special proforma was used to obtain sociodemographic, clinical, and laboratory variables of MetSy in diabetic participants. Blood pressure and anthropometric measurements such as waist circumference (WC) and body mass index (BMI) were measured. Fasting venous blood was collected to analyze biochemical variables such as fasting blood sugar (FBS), TG, and high-density lipoprotein-cholesterol (HDL-C). The microvascular complications of T2DM were established using fundus ophthalmoscopy and neurological and kidney function assessments with the help of laboratory tests. These variables were matched between MetSy and no MetSy groups along with the presence or absence of diabetes microvascular complications. This information was analyzed based on these assessments and patient interviews.ResultsOf the 160 T2DM patients, the mean age was 52 years with a predominance of females (51.8%) in the 50-59-year age group (56.8%). The average BMI for females was 29.38 ± 0.54 kg/m², and 32 (20%) had obesity. Females exhibited a large WC of 93.52 ± 1.58 cm, and 48 of 83 females had reported diabetes microvascular complications. A significant p-value was observed for hypertension, high TG, low HDL-C, large WC, obesity, BMI, age, and female gender on comparing diabetics with metabolic syndrome (MetSy+) and those without metabolic syndrome (MetSy-).The prevalence of microvascular complications in T2DM patients with MetSy+ was 52.5% compared with 47.5% in MetSy-. The prevalence of diabetic retinopathy was 24.9% (95% confidence interval (CI) = 20.3%-29.6%), nephropathy was 16.8% (95% CI = 12.8%-20.7%), and neuropathy was 10.8% (95% CI = 7.4%-13.3%).ConclusionsThe prevalence of MetSy observed among T2DM patients was 65%, with married obese females in the 50-59-year age group being more likely to be affected than males. Hypertension, poor glycemic control, high TG, low HDL-C, and greater anthropometric waist measurements and BMI were additional risk factors that tended to increase the MetSy burden in T2DM. Diabetic retinopathy, nephropathy, and neuropathy were the most prevalent microvascular complications of diabetes, and immediate attention is needed to stop their detrimental effects. Longer uncontrolled diabetes, increasing age, and hypertension were independent predictors of microvascular complications.To further reduce the risks of complications that threaten healthy aging and prognosis for these patients, MetSy screening, health education, and better diabetic management are crucial.

Microvascular complications are common among patients with diabetes mellitus (DM). The presence of heart failure (HF) is presumed to be due to macrovascular disease (typically HF with reduced ejection fraction [HFrEF] following myocardial infarction). We hypothesized that HF with preserved ejection fraction (HFpEF) in patients with DM may be a manifestation of microvascular disease compared with HFrEF. The objective of this study was to examine the prevalence and association with clinical outcome of microvascular complications in patients with HF and DM. We investigated the prevalence, association with clinical outcome, and cardiac structure and function of microvascular (neuropathy, nephropathy, and retinopathy) complications of DM in 2,800 prospectively enrolled participants with HF and DM (561 with HFpEF) from the Asian Sudden Cardiac Death In Heart Failure (ASIAN-HF) registry. A total of 601 (21.5%) participants with DM had microvascular complications. Participants with DM and any (one or more) microvascular complications were more likely to have HFpEF (odds ratio 1.70 [95% CI 1.15-2.50]; P = 0.008). Furthermore, the likelihood of having HFpEF increased with an increasing number of microvascular complications (P trend < 0.001). Microvascular complications were associated with more left ventricular (LV) hypertrophy and a greater reduction in quality of life in HFpEF than HFrEF (P interaction < 0.001 for all). Compared with participants with DM and without microvascular complications, the adjusted hazard ratio for the composite outcome of all-cause death or HF hospitalization was 1.35 (95% CI 1.04-1.76) for participants with DM and microvascular complications regardless of HF type (P interaction = 0.112). Diabetic microvascular disease is more common, and related to greater LV remodeling, more impairment of quality in life, and similar adverse outcomes, in participants with HFpEF compared with HFrEF. HFpEF may be a clinical manifestation of microvascular disease in DM.

Previous studies on the importance of metabolic syndrome (MS) as a cardiovascular risk factor had not focused on older Chinese adults. The present study analyzed the association of MS with carotid atherosclerosis and the risk of cardiovascular events in Chinese adults. Data of a representative cohort study with 5-year follow-up were used. Community-dwelling people (n=1257) aged ≥55 years without cardiovascular disease (CVD) at baseline were followed up from 2009 to 2014. MS was defined based on the Chinese Diabetes Society criteria under the Chinese Medical Association. Multiple regression analyses were performed to examine the associations of MS with atherosclerosis and CVD events, with adjustment for confounding factors. In a multivariate logistic regression model with adjustment, MS was closely related to common carotid artery intima-media thickness (CCA-IMT) (1.62; 95% CI: 1.19-2.21) and carotid plaque presence (1.38; 95% CI: 1.01-1.89), but not with carotid artery stenosis. At the end of the 5-year follow- up, compared with subjects without MS, hazard ratios and 95% confidence intervals for the different risks in subjects with MS were 1.86 (1.02-3.29) for myocardial infarction (MI), 1.39 (1.01-2.05) for stroke, 1.52 (1.02- 2.37) for CVD death, and 1.13 (0.62-2.58) for total death, after adjusting for age, gender, smoking, drinking, physical activity, uric acid, high-sensitivity C-reactive protein, dietary factors and carotid atherosclerosis status. MS was significantly associated with IMT and the presence of carotid plaque and with positively increased risks of MI, stroke, and CVD mortality independent of CVD risk factors in older Chinese adults.

The growing pandemic of childhood obesity has led to marked increases in the incidence and prevalence of type 2 diabetes mellitus (DM) and has further complicated the differentiation between type 2 and type 1 DM because more children with type 1 DM are overweight at time of diagnosis. In addition, numerous studies have demonstrated β-cell autoimmunity in children with type 2 DM. (1)After completing this article, readers should be able to:Type 2 diabetes mellitus (DM), historically considered a serious chronic medical condition only for older individuals, now has an increased prevalence in children and adolescents. The estimated overall incidence of type 2 DM is 22 cases per 100,000 youth or approximately 3600 youth diagnosed with the condition each year. (2) From a public health perspective, DM is the seventh leading cause of death in the United States, a figure that is likely underestimated. (3) The total cost to treat DM in both adults and children is approximately $174 billion per year, and medical expenses for individuals with diagnosed DM are 2.3 times higher than for those without DM. (3) The clinical and financial burdens of DM are increased by the complications and comorbidities of the disease. Because complications of DM develop and worsen during the disease, (2) it is important to effectively recognize and manage type 2 DM early when it is diagnosed during childhood and adolescence.DM represents a group of endocrine disorders characterized by hyperglycemia caused by defective insulin secretion, defective insulin action, or both. (4) The original division into 2 types was based on age at presentation and dependence on insulin. Now categories of DM (Table 1) are differentiated by their known underlying pathophysiologic characteristics. All forms of DM ultimately lead to hyperglycemia, although there may be overlap in the fundamental pathologic processes in each patient.Recent epidemiologic studies have demonstrated that more than 20% of new cases of DM in children and adolescents are due to type 2 DM. (5) The incidence of type 2 DM in children has increased in part because of the epidemic of childhood obesity and the associated insulin resistance, although the actual incidence of type 2 DM in children is likely higher than reported because of underdiagnosis.The incidence of type 2 DM increases with age. The SEARCH for Diabetes in Youth study demonstrated that the incidence of type 2 DM in children age 10 to 19 years was 42 per 100,000 youth compared with 1 in 100,000 youth among children age 0 to 9 years. (2) The peak age at onset of type 2 DM in children coincides with pubertal timing because the mean age at diagnosis is 12 to 16 years. (6) Females have a higher incidence of type 2 DM than males, (5) likely because girls are more insulin resistant and carry more subcutaneous fat than boys. (7)Type 2 DM disproportionately affects racial and ethnic minorities. American Indian youth have the highest incidence at 174 per 100,000. Black youth also have a particularly high incidence of 105 per 100,000 compared with 19 per 100,000 in non-Hispanic whites. (2)Epidemiologic studies report that children born to mothers with gestational diabetes are at greater risk of developing type 2 DM. (8) Breastfeeding appears to have protective effects against the development of type 2 DM. (9)The cause of type 2 DM is multifactorial, but the high concordance rate among monozygotic twins (1) and the frequent association with a family history of DM (10) suggest a genetic component. Between 74% and 100% of patients with type 2 DM have a first- or second-degree relative with the disease, in contrast to only 5% of patients with type 1 DM with a family history of type 1 DM. (6) Recent studies have identified multiple genetic loci that are associated with higher risk of type 2 DM. For example, polymorphisms in the TCF7L2 gene result in impaired insulin secretion and defective insulin processing, which confer a 1.4 times increased risk of type 2 DM. (1) More genetic markers are being identified with improvements in genetic testing.Glucose metabolism is tightly regulated by several processes, including sensing of glucose concentration, insulin synthesis, and secretion by pancreatic β-cells; suppression of hepatic glucose output; and insulin action on stimulated glucose uptake by the liver, intestines, and skeletal muscle. Hyperglycemia can result from derangements in any of these processes.Typically, type 1 DM and type 2 DM are conceptualized on a spectrum. Type 1 DM results from immune-mediated destruction of β-cells, leading to insulinopenia. Type 2 DM is the result of obesity-mediated insulin resistance and non–immune-mediated deficiency in insulin secretion.The pathogenesis of type 2 DM is complex and involves interactions between genetic and environmental factors. The core defect is varying degrees of insulin resistance and subsequent progressive insulinopenia. Other factors associated with obesity, such as elevated plasma free fatty acid concentrations and increased inflammatory markers, further inhibit β-cell insulin production and insulin-mediated glucose uptake. This leads to a cycle of worsening hyperglycemia and further metabolic derangement.A theory called the accelerator hypothesis suggests that obesity and weight gain contribute significantly to β-cell stress and confer earlier onset of all types of DM. Obesity is increasingly being accepted as a contributor to β-cell failure in genetically susceptible children, and increasing evidence suggests the influence of obesity in abnormal immune modulation. (1)During the past 30 years Americans have increased their total caloric intake by an additional 300 kcal/d. (11) Consumption of juices and sugar-sweetened beverages is a major source of these additional calories in the diet of children and adolescents (12) and is strongly associated with an increased risk of obesity and type 2 DM. (7) In addition, fewer children and adolescents are participating in recommended levels of physical activity.The association between lower birth weight and type 2 DM suggests that in utero programming may increase the risk of type 2 DM. (13) A thrifty-phenotype hypothesis suggests that poor fetal nutrition produces a postnatal metabolism that is adapted to poor but not plentiful nutrition. This programming contributes to insulin resistance and can predispose the development of type 2 DM in the context of excess nutrition and obesity. (14)Because up to 24% of children and adolescents with type 1 DM are overweight at diagnosis, (6) differentiating between type 2 DM and type 1 DM has become more difficult. (15) Further complicating the clinical delineation is the presence or absence of autoimmunity. The SEARCH for Diabetes in Youth Study measured the presence of glutamic decarboxylase (GAD) antibodies among diabetic patients. Positive GAD antibodies were found in 21% of patients with type 2 DM older than 10 years. (5) The Treatment Options for Type 2 DM in Adolescents and Youth (TODAY) study, a multicenter clinical trial, evaluated the presence of GAD and insulinoma-associated protein 2 antibodies. Of patients with diagnosed type 2 DM, 9.8% were antibody positive, 5.9% were positive for a single antibody, and 3.9% were positive for both antibodies. Those patients diagnosed as having type 2 DM who were antibody positive were more likely to be white and male and had a lower body mass index than antibody-negative patients. (16) A significant controversy exists regarding the classification of antibody-positive type 2 DM, with many authors maintaining that antibody-positive type 2 DM should be considered early type 1 DM and treated as such.The presenting symptoms of type 1 and type 2 DM can be similar and include polyuria, polydipsia, and polyphagia. Weight loss can be present in both types of DM. Clinical signs to suggest type 2 DM include overweight body habitus, with more than 85% of children with type 2 DM considered overweight or obese at the time of diagnosis. (6) Acanthosis nigricans, a darkened, thick, velvety appearance to the skin found typically in folds or creases, is present in 90% of patients with type 2 DM and can be the most easily visible clinical indicator of insulin resistance. (7) The frequency of acanthosis nigricans in obese adolescents or hyperinsulinemic children varies considerably by ethnicity. Up to 90% of obese or hyperinsulinemic children in Native American populations had acanthosis nigricans, whereas it was present in less than 5% of non-Hispanic white counterparts. (7) Clinicians can look for acanthosis nigricans in the nape of the neck, axilla, groin, and over flexor surfaces. The presence of ketoacidosis, normally found in patients with type 1 DM, does not rule out type 2 DM. Some reports indicate that up to 25% of children and adolescents with type 2 DM present with diabetic ketoacidosis. (17)Type 2 DM generally has a more insidious onset than type 1 DM, and many patients may be asymptomatic at presentation. However, because of the potentially long-standing hyperglycemia, patients may already have evidence of microvascular and macrovascular complications at the time of diagnosis. (10)Overall, the clinical distinction between type 1 DM and type 2 DM is increasingly obscured, especially with the increasing obesity pandemic. Clinicians must weigh the evidence to support their diagnosis and consider the potential outcomes of misclassification. In the case of significant hyperglycemia, diabetic ketoacidosis, and/or positive antibodies, it may be prudent to treat patients as having type 1 DM and wean insulin therapy if the future clinical course dictates.The criteria for diagnosis of DM were based on data to delineate risk for the development of retinopathy, a microvascular complication of DM, and are included in Table 2. (10) In 2009, an international expert committee convened and added an additional criterion for diagnosis, a hemoglobin A1c (HbA1c) level greater than 6.5% (0.07). (10)Indications to test for type 2 DM according to the Type 2 DM Consensus Panel are given in Table 3. Testing should begin at age 10 years or at the age of pubertal onset, whichever comes first, and should be repeated every 3 years. (18) The preferred method is to measure a fasting plasma glucose level, but a 2-hour plasma glucose level measured during an oral glucose tolerance test (OGTT) can be an alternative. (6)The American Diabetes Association (ADA) recommends that treatment of all children with DM should include routine follow-up every 3 months with a diabetes care team. (18) This team should include nutritional, psychological, and educational support and a medical professional experienced with DM care. The patient's self-management involves monitoring of blood glucose level, medication compliance, attention to dietary intake, and physical activity. Psychosocial considerations and medical compliance must also be addressed to ensure optimal success with therapy. The HbA1c level should be measured every 3 months during outpatient visits, and the goal HbA1c should be less than 7%. (18)(19)(20) Assessment of lipids, liver function tests, microalbuminuria, and signs and symptoms of sleep apnea should occur at diagnosis and annually. (19) Coordination between the diabetes care team and the primary care practitioner ensures a complete medical home for the child or adolescent.Treatment should be guided by the acuity of the clinical presentation. If a patient is acutely ketotic, dehydrated, or acidotic, intravenous hydration and insulin administration with inpatient admission are warranted. If the presentation is less acute, subspecialty referral, outpatient education, and use of oral medications can be initiated. Once the patient is clinically stable, treatment of type 2 DM is dually focused on weight management and minimizing complications associated with hyperglycemia.Lifestyle modification is an essential component of the management of type 2 DM and includes an emphasis on proper diet and exercise to maintain a healthy weight while preserving linear growth. For optimal management, lifestyle modification should be centered around the family unit and not strictly on individual patients. (20)Pharmacologic therapy addresses various aspects of the pathogenesis of type 2 DM (Figure) by reducing insulin resistance, increasing insulin secretion, slowing postprandial glucose absorption, or supplementing inadequate secretion of insulin. Metformin, a biguanide, is the only US Food and Drug Administration (FDA)–approved oral medication for treatment of type 2 DM in children older than 10 years and is considered first-line therapy in nonacute presentations. The mechanism of action is to decrease hepatic glucose production and enhance insulin-mediated glucose uptake in muscle and adipose cells. Adverse effects include transient abdominal pain, diarrhea, and nausea, although it is generally well tolerated. Metformin should not be given to patients with renal insufficiency, liver disease, or cardiac or respiratory insufficiency. Patients should be warned to discontinue metformin therapy before receiving intravenous contrast for radiographic studies because of the increased risk of lactic acidosis. In adults there is evidence that metformin can normalize blood glucose levels, decrease cholesterol levels, and reduce hypertension. Metformin can also be used to normalize ovulatory abnormalities in patients with polycystic ovarian syndrome. It is available in a liquid formulation and as an extended-release formulation, which can aid compliance and potentially reduce adverse effects. The recommended starting dose for metformin is 500 mg given orally once daily, with a maximum dose of 2000 mg per day.Insulin is used to attain early normalization of glycemic control, especially in patients who are acutely ill or have significant hyperglycemia, and insulin therapy should be started in all patients who present with diabetic ketoacidosis. Recent American Academy of Pediatrics clinical practice guidelines on the management of newly diagnosed type 2 DM recommend that insulin therapy be initiated in patients who have a random blood glucose level greater than 250 mg/dL (13.9 mmol/L) or whose HbA1c level is greater than 9%. (20) Once the diagnosis of type 2 DM is determined, insulin therapy can often be reduced as metformin therapy is initiated. Adverse effects of insulin can include weight gain from its anabolic effect on metabolism. Hypoglycemia, a potential adverse effect, is not as common among patients with type 2 DM.Other therapies, although not FDA approved for patients younger than 18 years, can be used by the diabetes management team to improve glycemic control. Sulfonylureas (glyburide, glipizide, and glimepiride) directly increase insulin secretion, so they are most useful when there is residual β-cell function. Major adverse effects include hypoglycemia and weight gain. Glucosidase inhibitors (acarbose and miglitol) reduce absorption of carbohydrates in the upper small intestine. They can lower HbA1c levels by 0.5% to 1%, and the major adverse effects are gastrointestinal intolerance and flatulence. Incretins (exenatide) are designed to increase postprandial insulin secretion. Exenatide is administered as a twice-daily injection. Adverse effects include nausea, vomiting, diarrhea, dyspepsia, jitteriness, dizziness, headaches, and hypoglycemia, especially if given with a sulfonylurea. Thiazolidinediones (rosiglitazone and pioglitazone) increase insulin sensitivity in muscle, adipose tissue, and the liver. In isolation, they can reduce HbA1c levels by 0.5% to 1.3%. Results from the TODAY study demonstrated that metformin in combination with rosiglitazone was more successful than metformin alone or metformin with lifestyle modification in preventing an increase in HbA1c levels above 8% (0.08). (20) There is some evidence that this combination may improve lipid profiles by lowering triglyceride levels and increasing high-density lipoprotein levels. (21) Adverse effects include edema, weight gain, and anemia and may infer additional cardiac risk (Figure).The risk of DM-related complications is directly related to the duration of disease. Prompt diagnosis and appropriate therapy are paramount in reducing this risk. Because of its insidious onset, many patients with type 2 DM have evidence of complications at the time of diagnosis. Among a sample of 100 Pima Indians with type 2 DM, 18% had hypertension, 7% had dyslipidemia, and 22% had microalbuminuria at the time of diagnosis. (22) Microvascular complications of type 2 DM include nephropathy, retinopathy, and neuropathy. Macrovascular complications include hypertension and hyperlipidemia, which can lead to cardiovascular disease. The ADA recommends that patients with type 2 DM have blood pressure measurements performed at every routine diabetes visit. (18) In the UK Prospective Diabetes Study, hypertension was found to be a more significant predictor of cardiovascular disease than blood glucose control. This study also found a 25% reduction in the risk of microvascular complications when the average HbA1c level decreased from 7.9% to 7.0%. (23)Patients should be screened for retinopathy with a dilated eye examination near the time of diagnosis and then yearly afterward. A lipid profile should be performed shortly after diagnosis, once glycemic control is attained, and should be performed annually thereafter. Urine microalbumin should be measured at diagnosis to assess for early nephropathy and followed up yearly. (18)Primary public health prevention efforts should target the general population to limit the prevalence of obesity. Secondary prevention should focus on screening those children who are at high risk for the development of type 2 DM (Table 2). Tertiary prevention in patients with type 2 DM should address reduction of complications.The authors wish to acknowledge Babalola Faseru, MD, MPH, assistant professor, Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, and Naim Mitre, MD, Naim Mitre, MD, medical director of clinical services, assistant fellowship program director, assistant professor of pediatrics, Division of Endocrine/Diabetes, Department of Pediatrics, University of Missouri-Kansas City/Children's Mercy Hospital.

On the basis of strong research evidence and consensus, type 1 diabetes mellitus (DM) remains the most common form of DM in children and adolescents. The incidence of type 2 DM in the pediatric population is rapidly increasing because of the obesity epidemic, and minority groups are disproportionately affected. (2) (10) (19) On the basis of some research evidence and consensus, it can be challenging to initially differentiate between type 2 DM and type 1 DM clinically because of the increased prevalence of obesity, the complex interplay of autoimmunity and obesity, and common symptoms at presentation. (1) (10) (19) Significant evidence and consensus support a genetic basis for the development of type 2 DM in children. Physicians should routinely screen at risk children older than age 10 years for DM. Screening criteria include obesity, a family history of type 2 DM, a minority racial or ethnic background, acanthosis nigricans, or other diseases associated with insulin resistance, including polycystic ovary syndrome, hypertension, or dyslipidemia. (1) (10) (18) (19) On the basis of consensus, diagnosis of type 2 DM can be confirmed by an elevated fasting blood glucose level greater than 126 mg/dl (7.0 mmol/L), an elevated 2-hour plasma glucose greater than 200 mg/dL (11.1 mmol/L) on an oral glucose tolerance test, an elevated random blood glucose greater than 200 mg/dL (11.1 mmol/L), or a hemoglobin A1c level greater than 6.5% with suggestive symptoms. (10) According to strong research evidence and consensus, once the diagnosis has been made, treatment should be based on the acuity of presentation and should focus on lifestyle modification and on normalizing hyperglycemia to minimize complications. Metformin is currently first-line treatment for type 2 DM in children and adolescents older than age 10 years who present nonacutely. (18) (19) Strong research evidence and consensus demonstrate that because type 2 DM has an insidious onset, microvascular and macrovascular complications can be present at the time of diagnosis. Patients should be screened for the presence of complications when the diagnosis of type 2 DM is made and in follow-up. (6) (10).

Obstructive sleep apnea syndrome (OSAS) may promote hyperglycemia and insulin resistance. We studied the link between sleep apnea and microvascular diabetic complications in veterans with type 2 diabetes mellitus (DM-2). A retrospective electronic chart of all veterans referred for sleep studies over a 1-year period was reviewed. Ninety-eight patients with a glycosylated hemoglobin < 6.5% were included in the study. The degree of glycemia (HbA1c) and presence of macro- and microvascular complications were compared with OSAS variables. Statistical analysis examined bivariate associations between OSAS variables and metabolic syndrome parameters. The apnea hypopnea index was significantly related to diabetic microvascular complications, particularly retinopathy. Oxygen desaturation was significantly and inversely related to microalbuminuria, microvascular complications, retinopathy, and HbA1c. Sleep apnea is associated with microvascular complications even in well-controlled DM-2 veterans. Screening for OSAS should be considered in patients with DM-2.

Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB (Houston Veterans Affairs Medical Center, Houston, Texas). Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 2005;54:533–539.

BACKGROUNDSurprisingly, it is estimated that about half of type 2 diabetics remain undetected. The possible causes may be partly attributable to people with normal fasting plasma glucose (FPG) but abnormal postprandial hyperglycemia. We attempted to develop an effective predictive model by using the metabolic syndrome (MeS) components as parameters to identify such persons.SUBJECTS AND METHODSAll participants received a standard 75-g oral glucose tolerance test, which showed that 106 had normal glucose tolerance, 61 had impaired glucose tolerance, and 6 had diabetes-on-isolated postchallenge hyperglycemia. We tested five models, which included various MeS components. Model 0: FPG; Model 1 (clinical history model): family history (FH), FPG, age and sex; Model 2 (MeS model): Model 1 plus triglycerides, high-density lipoprotein cholesterol, body mass index, systolic blood pressure and diastolic blood pressure; Model 3: Model 2 plus fasting plasma insulin (FPI); Model 4: Model 3 plus homeostasis model assessment of insulin resistance. A receiver-operating characteristic (ROC) curve was used to determine the predictive discrimination of these models.RESULTSThe area under the ROC curve of the Model 0 was significantly larger than the area under the diagonal reference line. All the other 4 models had a larger area under the ROC curve than Model 0. Considering the simplicity and lower cost of Model 2, it would be the best model to use. Nevertheless, Model 3 had the largest area under the ROC curve.CONCLUSIONWe demonstrated that Model 2 and 3 have a significantly better predictive discrimination to identify persons with normal FPG at high risk for glucose intolerance.

Diabetes mellitus is a non-communicable disease (NCD) with metabolic dysfunction that has attained epidemic proportions worldwide. Vascular complications account for the mortality and morbidity associated with diabetes. Hence, the study aimed to estimate the prevalence and risk factors for vascular complications in patients with type 2 diabetes mellitus (T2DM). A cross-sectional national multistage survey, the Saudi Health Interview Survey (SHIS), was used in this study, which surveyed individuals aged 15 years or older. After inclusion and exclusion criteria, 1240 diabetic patients' data were analyzed for sociodemographic data, risk factors, and prevalence of micro and macrovascular complications. Binary logistic regression with stepwise backward elimination was performed to build the optimal model to assess the determinants of macrovascular complications in diabetic patients. The strength of the associations was examined by estimating adjusted odds ratios (aOR) with their 95% CI. p-value < 0.05 was considered statistically significant. R Studio Version 1.2.1093 was used for statistical analysis RESULTS: Prevalence of micro and macrovascular complications in the diabetic patients was 6.05%, in which 3.5% had myocardial infarction, 1.2% had stroke and 1.9% had renal failure. The optimal model showed that for each year increase in age (aOR=1.05, 95%CI 1.02-1.07; p-value=0.000), smoking history (aOR=4.02, 95%CI 2.23-7.26; p-value=0.000), hypertensive patients (aOR=2.71, 95%CI 1.47-4.99; p-value=0.001), patients with low physical activity (aOR=4.32, 95%CI 1.26-14.82; p-value=0.001) were more likely to develop macro and microvascular complications in diabetic patients. The high prevalence of microvascular and macrovascular complications in diabetic patients poses a serious threat to public health in Saudi Arabia. A multisectoral approach needs to be undertaken to properly control and modify common risk factors at the community level.