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The dramatic rise in the incidence and prevalence of type 2 diabetes mellitus in the pediatric and adolescent populations has been associated with the ongoing epidemic of overweight, obesity, insulin resistance, and metabolic syndrome seen in these age groups. Although the majority of pediatric patients diagnosed with diabetes are still classified as having type 1 diabetes, almost 50% of patients with diabetes in the pediatric age range (under 18 years) may have type 2 diabetes. Screening of high-risk patients for diabetes and prediabetes is important. Prompt diagnosis and accurate diabetes classification facilitate appropriate and timely treatment and may reduce the risk for complications. This is especially important in children because lifestyle interventions may be successful and the lifelong risk for complications is greatest. Treatment usually begins with dietary modification, weight loss, and a structured program of physical exercise. Oral antidiabetic agents are added when lifestyle intervention alone fails to maintain glycemic control. Given the natural history of type 2 diabetes, most if not all patients will eventually require insulin therapy. In those requiring insulin, improved glycemic control and reduced frequency of hypoglycemia can be achieved with insulin analogs. It is common to add insulin therapy to existing oral therapy only when oral agents no longer provide adequate glycemic control.
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PMID:Diabetes screening, diagnosis, and therapy in pediatric patients with type 2 diabetes. 1892 36

The clinical correlates and risk profile of prediabetes (fasting plasma glucose (FPG) values in the upper normal limits but below the diabetic threshold) in hypertension, an insulin-resistant, prodiabetogenic condition, are scarcely known. For this reason, we evaluated 982 non-diabetic (FPG,<126 mg 100 ml(-1) and no antidiabetic treatment) referred hypertensive patients without a history of cardiovascular disease grouped by mild (100-109 mg 100 ml(-1)) and advanced (110-125 mg 100 ml(-1)) dysglycaemia compared with normal FPG (<100 mg 100 ml(-1)). FPG, total and high density lipoprotein (HDL) cholesterol, triglycerides and total white blood cell count were assessed by standard methodologies; 10-year predicted coronary heart disease (CHD) risk was approximated by the Framingham risk score (FRS). Metabolic syndrome (MetS) was diagnosed by standard categorical criteria using either 110 or 100 mg 100 ml(-1) as a threshold for impaired fasting glucose (IFG). FPG was above 110 in 13% and between 100 and 109 in 20% of patients. In both dysglycaemic groups, perturbed glucose homeostasis was associated with abnormally high fasting triglycerides, low HDL cholesterol, obesity, worse CHD risk profile and higher white blood cell count. MetS was highly prevalent and its distribution pattern was markedly influenced by the definitions of IFG based on different FPG cutoffs. Thus, even mildly perturbed glucose homeostasis associates with atherogenic dyslipidaemia, obesity and adverse risk profile in non-diabetic hypertensive patients. Because of its prediabetic nature, dysglycaemia should prompt measures to prevent new-onset diabetes, although the role of IFG as an independent risk factor awaits specifically designed intervention trials.
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PMID:Dysglycaemia in non-diabetic hypertensive patients: comparison of the impact of two different classifications of impaired fasting glucose on the cardiovascular risk profile. 1907 90

Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy. In fact, diabetes subjects are more prone to develop extense and earlier-than-usual leukoaraiosis (White Matter High-Intensity Lesions - WMHL). WMHL are usually present at different degrees in brain scans of elderly people. People with more advanced WMHL are at increased risk for executive dysfunction, cognitive impairment and dementia. Clinical phenotypes associated with insulin resistance possibly represent true clinical models for brain and systemic aging.
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PMID:(Pre)diabetes, brain aging, and cognition. 1913 49

In this study, our aim was to investigate the associations between diet quality and newly diagnosed diabetes, prediabetes, and cardio-metabolic risk factors. The analysis was based on 7441 participants of the Australian Diabetes, Obesity and Lifestyle study, a cross-sectional study of adults aged > or =25 y involving a 75-g oral glucose tolerance test. Diet quality was assessed via a dietary guideline index and FFQ data. Associations between diet quality and diabetes, prediabetes (impaired fasting glycemia, impaired glucose tolerance), and cardiovascular risk factors were investigated using linear and logistic regression adjusted for age, education, smoking, physical activity, sedentary behavior, and BMI. Higher diet quality was significantly associated with lower systolic and diastolic blood pressure among men, lower fasting plasma glucose among men and women, and lower systolic blood pressure, fasting plasma insulin, and 2-h plasma glucose and greater insulin sensitivity among women. Diet quality was inversely associated with abdominal obesity [odds ratio (OR) for top quartile: 0.68, 0.48-0.96], hypertension (OR: 0.50, 0.31-0.81), and type 2 diabetes (OR: 0.38, 0.18-0.80) among men. Lack of compliance with established dietary guidelines was associated with type 2 diabetes and cardio-metabolic risk factors. Further work is required to determine whether this dietary index has predictive validity for health in longitudinal studies.
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PMID:Dietary quality is associated with diabetes and cardio-metabolic risk factors. 1921 25

There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.
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PMID:Adverse metabolic and cardiovascular consequences of circadian misalignment. 1927 18

Careful selection of bariatric patients is critical for successful outcomes. In 1991, the NIH first established patient selection guidelines; however, some surgeons operate on individuals outside of these criteria, i.e., extreme age groups. We developed appropriateness criteria for the spectrum of patient characteristics including age, BMI, and severity of eight obesity-related comorbidities. Candidate criteria were developed using combinations of patient characteristics including BMI: > or =40 kg/m(2), 35-39, 32-34, 30-31, <30; age: 12-18, 19-55, 56-64, 65+ years old; and comorbidities: prediabetes, diabetes, hypertension, dyslipidemia, sleep apnea, venous stasis disease, chronic joint pain, and gastroesophageal reflux (plus severity level). Criteria were formally validated on their appropriateness of whether the benefits of surgery clearly outweighed the risks, by an expert panel using the RAND/UCLA modified Delphi method. Nearly all comorbidity severity criteria for patients with BMI > or =40 kg/m(2) or BMI = 35-39 kg/m(2) in intermediate age groups were found to be appropriate for surgery. In contrast, patients in the extreme age categories were considered appropriate surgical candidates under fewer conditions, primarily the more severe comorbidities, such as diabetes and hypertension. For patients with a BMI of 32-34, only the most severe category of diabetes (Hgb A1c >9, on maximal medical therapy), is an appropriate criterion for those aged 19-64, whereas many mild to moderate severity comorbidity categories are "inappropriate." There is overwhelming agreement among the panelists that the current evidence does not support performing bariatric surgery in lower BMI individuals (BMI <32). This is the first development of appropriateness criteria for bariatric surgery that includes severity categories of comorbidities. Only for the most severe degrees of comorbidities were adolescent and elderly patients deemed appropriate for surgery. Patient selection for bariatric procedures should include consideration of both patient age and comorbidity severity.
Obesity (Silver Spring) 2009 Aug
PMID:Appropriateness criteria for bariatric surgery: beyond the NIH guidelines. 1934 19

Microvascular complications are an important cause of morbidity in diabetic patients and can be detected in a significant number of patients at the time of diabetes diagnosis. However, little is known about the alterations in the microvasculature previous to the clinical manifestation of diabetes mellitus type 2. To obtain more insights into the early microvascular deterioration resulting from prediabetes, morphological and functional microvascular parameters were monitored using intravital fluorescence microscopy through a dorsal skin-fold chamber preparation in the uncoupling promotor-driven diphtheria toxin A chain (UCP1/DTA) mice. At the age of 12 weeks, the UCP1/DTA-mice were characterized by impaired glucose tolerance with concurrent unchanged fasting glucose, as well as dyslipidemia, hyperinsulinemia, hypertension and obesity. Prediabetic mice displayed combined hypertriglyceridemia and hypercholesterinemia. Associated with these prediabetic metabolic alterations, we demonstrate that microvascular density showed a dramatic decrease due to a reduction in perfused small vessels. A reduction in vascular density combined with unaltered blood flow in single vessels resulted in impaired tissue perfusion. Endothelial dysfunction with subsequently increased microvascular permeability and leukocyte-endothelium interactions were found. Our results of profound microvascular alterations at stages of normal fasting glucose underline the importance of early screening for prediabetes and associated microvascular complications.
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PMID:Early microvascular complications of prediabetes in mice with impaired glucose tolerance and dyslipidemia. 1936 64

Condition prior to diabetes is designated as prediabetes. The use of this term is recommended if fasting plasma glucose exceeds normal level but does not reach the characteristic result of real diabetes. Prediabetes is often characterized by combination of visceral obesity, glucose and lipid metabolism disorders and changes in blood pressure. Change of life style is more important in the treatment of prediabetes associated hypertension than in other hypertensive diseases. In this case, metabolically neutral antihypertensive medication is the treatment of choice. The growing obesity epidemic underlines the significance of prediabetes associated hypertension in public health. While 25% of the adult population suffering from this kind of hypertensive disease, the optimal solution has to be found together with patients, physicians and the money lenders of the social security system.
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PMID:[Treatment of hypertension associated with prediabetes]. 1942 89

Type 2 diabetes mellitus (T2DM) in children and adolescents is an important Public Health problem against the backdrop of the epidemic of childhood obesity. The clinical presentation of T2DM in youth is heterogeneous from minimal symptomatology to diabetic ketoacidosis. The increasing rates of youth T2DM have paralleled the escalating rates of obesity, which is the major risk factor impacting insulin sensitivity. Additional risk factors include minority race, family history of diabetes mellitus, maternal diabetes during pregnancy, pubertal age group and conditions associated with insulin resistance (IR) - such as polycystic ovary syndrome (PCOS). The pathophysiology of T2DM has been studied extensively in adults, and it is widely accepted that IR together with beta-cell failure are necessary for the development of clinical diabetes mellitus in adulthood. However, pathophysiologic studies in youth are limited and in some cases conflicting. Similar to adults, IR is a prerequisite, but beta-cell failure is necessary for progression from normal glucose tolerance to prediabetes and frank diabetes in youth. Even though rates of T2DM in youth are increasing, the overall prevalence remains low if compared with type 1 diabetes mellitus (T1DM). However, as youth with T1DM are becoming obese, the clinical distinction between T2DM and obese T1DM has become difficult, because of the overlapping clinical picture with evidence of islet cell autoimmunity in a significant proportion of clinically diagnosed youth with T2DM. The latter are most likely obese children with autoimmune T1DM who carry a misdiagnosis of T2DM. Further research is needed to probe the pathophysiological, immunological, and metabolic differences between these two groups in the hopes of assigning appropriate therapeutic regimens. These challenges combined with the evolving picture of youth T2DM and its future complications provide unending opportunities for acquisition of new knowledge in the field of childhood diabetes.
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PMID:Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon. 1946 9

The data from blood glucose meters are discontinuous, providing only an estimate of the "amount" of glucose. Continuous sensors provide time series data, including "amount," but adding direction, rate of change, and rate of acceleration. Currently, continuous sensor labeling requires a fingerstick confirmation for treatment decisions and for periodic calibration. Because of the added information, sensors may be as efficacious and safe as meters when used for treatment decisions but have not yet been tested in stand-alone mode. Glucose sensors are currently in the early adopter's phase of technology development. To extend to the broader diabetes patient population, improvements are needed in reliability, comfort, ease of use, and integration with other technologies. In order to achieve a closed loop (artificial pancreas), the "Holy Grail" of the diabetes device industry, improvements in the accuracy of continuous sensors are also required. The main source of sensor inaccuracy is the calibration process. Calibration updates during the sensor wear period are required because of the gross changes in local metabolism (during the formation of the foreign body response) around the sensors after insertion and during the entire period of wear. Ambulatory sensors are currently approved and used only to treat insulin-using diabetes patients. In the future, the technology may have benefit for diagnostic use and behavior modification in obesity, metabolic syndrome, and prediabetes, as well as metabolic monitoring in elite athletes, soldiers, pilots, and the like. Hospitals currently use single-point information for tracking glucose in patients. Blood-based continuous sensing may provide the data needed to prevent in-hospital hypoglycemia and may lead to closed loop technology in the hospital.
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PMID:Continuous glucose sensing: future technology developments. 1946 75


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