Type 2 Diabetes and its Association with Hypertension and Depression in an Iraqi Population

Objective To study the association of TCF7L2 gene rs11196218,rs290487 polymorphisms with metabolic syndrome in type 2 diabetes mellitus population.Methods According to the diagnostic criteria of international diabetes federation (IDF),680 cases of type 2 diabetes patients were divided into metabolic syndrome (MS) group and non metabolic syndrome (control) group.DNA was extracted from peripheral mononuclear cells,and then PCR was performed to specifically amplify TCF7L2 gene fragments.Gene polymorphisms were determined by connected enzyme detection reaction.After population representative was checked by Hardy-Weinberg equilibrium,statistical analysis was completed by software SPSS 13.0.Results The population was accorded with Hardy-Weinberg equilibrium and possessed the population representative.Frequency distributions of genotypes (GG,AG and AA) in TCF7L2 gene rs11196218 in MS and control groups were 55.6％(233/419),35.8％(150/419),8.6％ (36/419) and 54.8％ (126/230),39.1％ (90/230),6.1％ (14/230),respectively.Frequency distributions of alleles(G and A) in TCF7L2 gene rs11196218 in MS and control groups were 73.5％(616/838),26.5％(222/838)and 74.3％(342/460),25.7％(118/460),respectively.Frequency distributions of genotypes (GG,AG and AA) in TCF7L2 gene rs290487 in MS and control groups were 14.8％(62/418),42.3％(177/418),42.9％(179/418) and 15.0％(34/226),48.2％(109/226),36.8％(83/226),respectively.Frequency distributions of alleles(G and A) in TCF7L2 gene rs11196218 in MS and control groups were 36.0％ (301/836),64.0％ (535/836) and 39.1％ (177/452),60.9％ (275/452),respectively.Frequency distribution of allele and genotype in TCF7L2 genes rsl 1196218 and rs290487 between the two groups were not associated with metabolic syndrome in type 2 diabetes population (P ＞ 0.05).Conclusions TCF7L2 gene rs11196218,rs290487 polymorphisms has not association with metabolic syndrome of type 2 diabetes. Key words: Type 2 diabetes; Metabolic syndrome; TCF7L2; Polymorphism

The metabolic syndrome (MetS), a cluster of metabolic abnormalities with insulin resistance as a major characteristic, has gone by several names over the past two decades. The diagnostic criteria proposed by the Adult Treatment Program III (ATP III) of the National Cholesterol Education Program (NCEP) have led to greater awareness of the components and treatment strategies.1 Five diagnostic traits are listed in the ATP III version of the MetS (Table; referred to as the “metabolic syndrome”), and the presence of any 3 of these factors is considered sufficient for diagnosis. This practical review will consider each in turn, providing advice for cardiologists, internists, and other health care providers who are diagnosing and treating persons with the syndrome in an effort to prevent a variety of clinical outcomes. View this table: Diagnostic Criteria for the Metabolic Syndrome The major adverse consequence of the MetS is cardiovascular disease (CVD). Several of the metabolic abnormalities associated with the syndrome, in fact, are CVD risk factors. One of these abnormalities, insulin resistance, also predisposes to the development of type 2 diabetes mellitus (T2DM). In age-adjusted estimates from the National Health and Nutrition Examination Survey III in 1998 to 1994, approximately 24% of adult Americans had ≥3 of the 5 MetS criteria. Key determinants of greater prevalence were age and ethnicity. Prevalence rates were highest in Mexican Americans and were successively lower in white, African American and other racial groups.2 These published estimates included persons with diabetes mellitus who had met the 1998 fasting glucose criteria (≥126 mg/dL [8.0 mmol/L]) of the American Diabetes Association.3 This article will focus on the features of the MetS in persons without diabetes mellitus, although most persons with T2DM also have the MetS. Moreover, the therapeutic approaches to metabolic risk factors described here also can be applied to …

Background. The prevalence of metabolic syndrome (MS) among people with type 1 diabetes mellitus (T1DM) varies widely depending on the criteria used and ranges from 6.4 to 57%. The relevance of studying the MS in T1DM is caused by the high risk of developing of micro and macrovascular complications. The current criteria for MS and the controversy over the inclusion of T1DM as a criterion do not provide reliability in diagnosing MS in this disease.The aim. To assess the prevalence of MS in adults with T1DM and its impact on the course of the disease.Materials and methods. A total of 134 patients over the age of 18 years were studied, including 67 (50%) men and 67 (50%) women. The median age was 33[19; 43] years, the median duration of diabetes was 13 [4; 27] years. MS was assessed according to the criteria of the 2009 Joint Interim Statement (JIS).Results. MS was detected in 34 (25.4%) patients. The number of patients who did not have other criteria for MS except for T1DM was 57 (42.5%), 43 (32.1%) patients had 2 components of MS (one of the components in all was diabetes). Waist circumference >94 cm in men and > 80 cm in women, as well as blood pressure > 130 and 85 mm Hg were the most common components of MS (73.5 and 70.6% respectively). The insulin sensitivity coefficient was significantly lower in the group of people with MS (p=0.012). In patients with MS, only diabetic nephropathy was significantly more common (p = 0.019), while the differences in the frequency of retinopathy and neuropathy were statistically insignificant.Conclusion. MS is a common condition in T1DM, which is based on insulin resistance. Presence of MS is associated with a risk of developing of diabetic nephropathy.

Abdominal obesity is closely associated with the presence of metabolic risk factors and elevated blood pressure in selected materials. This has, however, never been analyzed quantitatively in a non-selected cohort. Therefore, in a population-based study of 1462 Swedish women, four selected risk factors for non-insulin dependent diabetes mellitus (NIDDM) and cardiovascular disease (CVD), serum triglycerides, blood glucose and systolic blood pressure and also serum insulin in a subsample, were examined in relation to regional and overall obesity. This was performed by subdividing the age adjusted sample into quintiles of waist to hip circumference ratio (WHR) or body mass index (BMI) as indicators of abdominal distribution of body fat and overall obesity, respectively. The risk factors serum triglycerides, blood glucose, blood pressure and serum insulin were defined as being elevated when the value of the risk factor was higher than the mean plus one or two standard deviations of the total age-adjusted cohort. The percentage of women with elevated risk factors according to this definition was then calculated in each of these quintiles. Having a risk factor which was elevated according to the definition was significantly correlated to WHR and BMI (p<0.0001) independent of age. The presence of one or several of these elevated risk factors was clearly higher than expected in the fifth quintile of WHR, and to a lesser extent in the fifth quintile of BMI while this was not the case in the lower quintiles of WHR and BMI. When studying the combination of the WHR and BMI, the presence of risk factors higher than the mean plus two standard deviations increased gradually with WHR in all five quintiles of BMI. A significant association was observed between WHR and presence of risk factors independent of BMI (p<0.0001) but BMI did not remain significantly correlated to presence of risk factors when controlling for WHR (p=0.09). These results indicate that abdominal distribution of body fat in women independently of general obesity is closely associated with metabolic risk factors including elevated blood pressure, a metabolic syndrome with increased risk for cardiovascular disease and non-insulin dependent diabetes mellitus.

FABP4 plasma levels are increased in familial combined hyperlipidemia

Preventable Coronary Heart Disease Events from Control of Cardiovascular Risk Factors in US Adults With Diabetes (Projections from Utilizing the UKPDS Risk Engine)

Type 2 diabetes mellitus (T2DM) in children and adolescents is becoming an increasingly important public health concern throughout the world (1–17). Because of the relatively recent recognition of the problem in this age group, many children with new onset T2DM may be misclassified as having T1DM. Conversely, as the population becomes heavier, overweight adolescents with autoimmune diabetes may be misdiagnosed as having T2DM. T2DM is often associated with risk factors for cardiovascular disease that may already be present at the time of diagnosis, making normalization of blood glucose levels and diagnosis and treatment of hypertension and dyslipidemia important (18). T2DM occurs when insulin secretion is inadequate to meet the increased demand posed by insulin resistance (19). Thus, T2DM is commonly associated with other features of the insulin resistance syndrome [hyperlipidemia, hypertension, acanthosis nigricans, ovarian hyperandrogenism, non-alcoholic fatty liver disease (NAFLD)] (20). Insulin secretion depends on disease status and duration, and can vary from delayed but markedly elevated in response to a glucose challenge, to absolutely diminished (19). Adults with symptoms have 50% reduction at the time of diagnosis, and may become insulin dependent within a few years (21). T2DM occurs: in youth most often during the second decade of life, with a mean age of diagnosis of ∼13.5 years. This coincides with the peak of physiologic pubertal insulin resistance, which may lead to onset of overt diabetes in previously compensated adolescents. in all races, but at a much greater prevalence in those of non-white European descent, e.g. those of black African descent, native North American, Hispanic (especially Mexican)-American, Asian, South Asian (Indian Peninsula), and Native Pacific islanders. The SEARCH for Diabetes in Youth population-based study found the proportion of physician diagnosed T2DM among 10–19-year-olds to vary greatly by ethnicity in the US: 6% for non-Hispanic whites, 22% for Hispanics, 33% for blacks, 40% for Asians/Pacific Islanders, and 76% for Native Americans (8). In Hong Kong > 90% of young onset diabetes is T2DM (10), in Taiwan 50% (11) and nearly 60% in Japan (Ogawa et al. personal communication). in > 75% of cases in youth in the USA there is a first or second-degree relative with T2DM. in youth in the USA and Europe with body mass index (BMI) above 85th percentile for age and sex. In Japan, however, ∼30% of T2DM are not obese (17), in Asian Indian urban children, half of those with T2DM had normal weight (< 120% ideal for height) (12), and half of Taiwanese children with T2DM were not obese (11). in some asymptomatic individuals in high-risk populations during medical, school, or sports examinations (22,23). in the presence of ketosis/ketoacidosis, one third or more of newly diagnosed patients (24). This presentation is responsible for misclassification of T2DM patients as T1DM. occasionally with severe dehydration (hyperosmolar hyperglycemic coma, hypokalemia) at presentation, which can be fatal (24,25) with a sex ratio (male:female) that varies from 1: 4–1:6 in native North Americans to 1:1 in Asians and Libyan Arabs without associated HLA specificities. without associated islet cell autoimmunity (see autoimmunity T2DM). The pathophysiology of autoimmune 'T2DM' is unclear. It most likely represents autoimmune T1DM in overweight or obese individuals with underlying insulin resistance. It has been postulated that obesity and insulin resistance may promote an inflammatory response to antigen exposure caused by apoptosis of beta cells (26). Youth and adults in US and Europe who are clinically diagnosed with T2DM are found to have T1DM-associated auto-antibodies in 15–40% of cases, including many who are not receiving insulin one year after diagnosis (27–30). Antibody positive young adult individuals with the T2DM phenotype are significantly less overweight and younger than antibody negative patients (21, 27). Hemoglobin (HbA1c) concentrations are significantly higher in young adults with T2DM who are antibody positive compared with those who are antibody negative (27). ß-cell function is significantly less in antibody positive individuals, the most dramatic difference being reported in younger adult patients (25–34 years), resulting in more rapid development of insulin dependence, usually by 3 years duration (27, 30). The presence of islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies in adults with clinically typical T2DM has been referred to as latent autoimmune diabetes of adults (27, 31). Neither the autoimmunity nor the diabetes is latent, however (26). Atypical diabetes mellitus (ADM) occurs throughout childhood, but rarely begins past age 40. It has only been described in young people of African descent. There is a strong family history in multiple generations with an autosomal dominant pattern of inheritance, but an abnormal sex ratio (M : F = 1 : 3). ADM is not associated with HLA specificities and islet autoimmunity does not occur. Ketosis or ketoacidosis is typical at onset. Insulin secretion is present but diminished and without long-term deterioration of function. Interestingly, insulin is often not required for survival after treatment of acute metabolic deterioration, although diabetes control may be poor and ketoacidosis may recur without insulin, e.g. with illness or pregnancy. ADM is not associated with obesity beyond that in the general population and it is not associated with insulin resistance. Monogenic diabetes (formerly referred to as maturity onset diabetes of the young or MODY) For more in depth information see the ISPAD Clinical Consensus Guidelines for Monogenic Diabetes (34). Identified in families with multigenerational diabetes; including asymptomatic individuals identified through testing of family members. Monogenic diabetes is not associated with obesity beyond that in the general population and it is not associated with insulin resistance The clinician is obliged to weigh the evidence in each individual patient to distinguish between T1DM and T2DM. The reasons for this conundrum are: with increasing obesity in childhood, as many as 15–25% of newly diagnosed T1DM (or monogenic diabetes) patients may be obese. the significant number of pediatric patients with T2DM demonstrating ketonuria or ketoacidosis at diagnosis (2). T2DM is common in the general adult population, with a random family history of ∼15% or greater in minority populations, reducing the specificity of a positive family history. positive family history for T2DM is increased for patients with T1DM as much as threefold over the non-diabetic population and T1DM is more frequent in relatives of patients with T2DM (35, 36). There is considerable overlap in insulin or C-peptide measurements between T1DM, T2DM and MODY at onset of diabetes and over the first year or so. This overlap is due to the recovery phase of autoimmune-mediated T1DM (the honeymoon) and degree of glucotoxicity/lipotoxicity impairing insulin secretion at the time of testing in both T1DM and T2DM. In addition the insulin resistance of obesity raises residual C-peptide levels in obese adolescents with T1DM. Such measurements are thus relatively valueless in the acute phase. [The role of C peptide may be more helpful in established diabetes as persistent elevation of C-peptide above the level of normal would be unusual in T1DM after 12–24 months.] The criteria and classification of diabetes are presented in greater detail in the ISPAD Clinical Practice Consensus Guidelines: Definition, Epidemiology, Diagnosis and Classification of Diabetes (37) Diagnostic criteria for diabetes are based on BG measurements and the presence or absence of symptoms (E) (38,39). Three ways to diagnose diabetes are possible and each, in the absence of unequivocal hyperglycemia, must be confirmed, on a subsequent day, by any one of the three methods given below. Diabetes is diagnosed when: A fasting plasma glucose (FPG) is ≥ 7.0 mmol/l (126 mg/dl) or The post challenge plasma glucose is > 11.1 mmol/l (200 mg.dl) performed as described by the World Health Organization (39), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. or Symptoms of diabetes and a casual plasma glucose ≥ 200 mg/dl (11.1 mmol/L). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. Diabetes in children, including T2DM, usually presents with characteristic symptoms such as polyuria, polydipsia, blurring of vision, and weight loss, in association with glycosuria and, in some cases, ketonuria. In its most severe form, ketoacidosis or hyperglycemic hyperosmolar state may develop and lead to stupor, coma, and in absence of effective treatment, death. The diagnosis is usually confirmed quickly in symptomatic individuals by measurement of a marked elevation of the blood glucose level. In this situation, if ketones are present in the blood or urine, treatment is urgent. Waiting another day to confirm the hyperglycemia may be dangerous in allowing ketoacidosis or hyperosmolarity to evolve. In the absence of symptoms or presence of mild symptoms of diabetes, hyperglycemia detected incidentally or under conditions of acute infective, traumatic, circulatory, or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes. The diagnosis of diabetes, in the absence of symptoms, should not be based on a single plasma glucose concentration. Diagnosis may require continued observation with fasting and/or 2-h postprandial BG levels and/or an oral glucose tolerance test (OGTT). An OGTT should not be performed if diabetes can be diagnosed using fasting, random, or postprandial criteria, as excessive hyperglycemia can result using a fasting OGTT in these circumstances. (E). If doubt remains, periodic re-testing should be undertaken until the diagnosis is established or refuted. There are individuals whose glucose levels do not meet the criteria for diabetes, but are too high to be considered normal. Impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) are intermediate stages in the natural history of disordered carbohydrate metabolism between normal glucose homeostasis and diabetes (E). IFG and IGT are not interchangeable and represent different abnormalities of glucose regulation. IFG is a measure of disturbed carbohydrate metabolism in the basal state, while IGT is a dynamic measure of carbohydrate intolerance after a standardized glucose load. Patients with IFG and/or IGT are now referred to as having 'pre-diabetes', indicating the relatively high risk for development of diabetes in these patients (38). IFG and IGT may be associated with the metabolic syndrome (MS), which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-high density lipoprotein type, and hypertension. Individuals who meet the criteria for IGT or IFG may be euglycemic in their daily lives as shown by normal or near-normal glycated hemoglobin levels, and those with IGT may manifest hyperglycemia only when challenged with an OGTT. FPG < 5.6 mmol/L (100 mg/dL)= normal fasting glucose. FPG 5.6–6.9 mmol/L (100–125 mg/dL)= IFG. FPG ≥ 7.0 mmol/L (126 mg/dL)= provisional diagnosis of diabetes (the diagnosis must be confirmed, as described above under 'Diagnostic criteria for type 2 diabetes'). The corresponding categories for IGT when the OGTT is used are as follows: 2-h postload glucose < 7.8 mmol/l (140 mg/dl)= normal glucose tolerance. 2-h postload glucose 7.8–11.1 mmol/l (140–199 mg/ dl)= IGT. 2-h postload glucose > 11.1 mmol/l (200 mg/dl)= provisional diagnosis of diabetes (the diagnosis must be confirmed with additional testing, as described above). After the diagnosis of diabetes is established, autoantibody testing should be considered when diagnosing and treating T2DM. Diabetes autoantibody testing should be considered in all pediatric patients with the clinical diagnosis of T2DM because of the high frequency of islet cell autoimmunity in otherwise "typical" T2DM. Antibodies will indicate an earlier need for insulin as well as the need to monitor for thyroid autoimmunity and to consider other autoimmune disorders associated with T1DM. (E) Diabetes autoantibody testing also should be considered in overweight/obese children > 13 years of age with a clinical picture of T1DM (weight loss, ketosis/ketoacidosis), some of whom may have T2DM (E) Insulin resistance is an impaired response to the physiologic effects of insulin, including effects on glucose, lipid, and protein metabolism, and on vascular endothelial function. Insulin resistance occurs in most tissues including liver, muscle, and fat tissue and is influenced by sex, age, race/ethnicity, stage of sexual maturation, and total adiposity. While visceral adiposity is important in insulin resistance in adults, the specific contribution of visceral adiposity to insulin resistance in the pediatric population remains uncertain. Several events in development may be associated with increased risk for the insulin resistance syndrome. These include premature adrenarche in girls (pubic hair appearing before the age of 8 years) and being born small for gestational age. Girls with a history of premature adrenarche are at increased risk for ovarian hyperandrogenism and PCOS and thus, insulin resistance (40). Children born small for gestational age are at increased risk for insulin resistance related to decreased intrauterine growth (41) and also at increased risk for premature adrenarche. Diabetes is only one manifestation of the insulin resistance syndrome or the MS (22, 42–50). Other associations include: Obesity: Obesity has deleterious associations with morbidity and cardiovascular risk independent of effects related to insulin resistance and diabetes (51–54). Nephropathy: Albuminuria (either micro- or macro- ) is present at the time of diagnosis in a substantial number of adolescents with T2DM and prevalence increases with duration of diabetes (24). Proteinuria and focal segmental glomerular sclerosis have also been reported in African-American adolescents with severe obesity, in the absence of diabetes (55). Hypertension; Hypertension is estimated to account for 35–75% of diabetes complications, both microvascular and macrovascular (56). Diabetes or impaired glucose tolerance doubles the risk of developing hypertension (57). In addition, there is a possible genetic predisposition to hypertension in T2DM related to the associated angiotensin converting enzyme genotype (58). Hypertension in T2DM is due to volume expansion and increased vascular resistance (59) related to reduced (NO)-mediated vasodilatation and increased activity of the renin-angiotensin system. Dyslipidemia: Hypertriglyceridemia and decreased high-density lipoprotein cholesterol are the hallmarks of T2DM dyslipidemia. Additional findings include elevated very low-density lipoprotein (VLDL), elevated LDL-c, elevated lipoprotein(a), and increased small dense LDL particles. Decreased lipoprotein lipase activity, increased lipoprotein glycation and increased lipoprotein oxidation render the lipoproteins more atherogenic. (60,61) Ovarian hyperandrogenism and premature adrenarche (62): PCOS is being increasingly recognized in adolescents as part of the insulin resistance syndrome. Adolescents with PCOS have ∼40% reduction in insulin-stimulated glucose disposal compared to body composition matched non-hyperandrogenic control subjects (59). Decreasing insulin resistance may improve ovarian function and increase fertility. NAFLD: Hepatic steatosis is present in 25–45% of adolescents with T2DM and more advanced forms of NAFLD, such as non-alcoholic steatohepatitis, are increasingly common and associated with progression to cirrhosis (24, 64). NAFLD now represents the most common cause of cirrhosis in children and the most common reason for liver transplantation in adults in the US. Systemic inflammation: elevated C-reactive protein, inflammatory cytokines and white blood cell counts in obese adolescents have been associated with increased risk for cardiovascular disease in adults (54). Additional health problems related to obesity include Obstructive sleep apnea (OSA) with associated pulmonary hypertension (65), orthopedic problems resulting in diminishing physical activity (66,67), pancreatitis, cholecystitis and pseudotumor cerebri. In adults, there is a strong association between level of hyperglycemia and increased risk of macrovascular disease. Hyperglycemia, dyslipidemia, and hypertension are contributors to the acceleration of atherosclerosis in T2DM, along with oxidative stress, glycation of vascular proteins, and abnormalities of platelet function and coagulation. Defective endothelium dependent vasodilatation is an additional factor accelerating atherosclerosis in T2DM. It is an early sign of increased risk for cardiovascular disease, and predictive of cardiovascular events (68) (B) and occurs in obese children relative to their level of obesity and degree of insulin resistance (69) (B). Co-morbidities characteristic of the insulin resistance syndrome are commonly seen at diagnosis or appear early in the course of T2DM and should be tested for sooner than in T1DM, where these disorders are complications of the diabetes rather than co-morbid conditions (70, 71) (B). A more complete discussion of testing for complications/co-morbidities is presented in the ISPAD Clinical Practice Guidelines for microvascular and macrovascular complications (72). Either micro- or macro-albuminuria, may be present at the time of diagnosis and albuminuria should be evaluated at diagnosis and annually thereafter (55, 72)(E). Likewise, hypertension may be present at, or prior to diagnosis of diabetes and each individual should be evaluated at every visit for hypertension. Dyslipidemia is more common in type 2 diabetes and in family members, (60,61) and should be screened for when metabolic stability is achieved. Evaluation for NAFLD should be done at diagnosis and annually thereafter (24)(E). Inquiries about puberty, menstrual irregularities and obstructive sleep apnea should be made at diagnosis and regularly thereafter (65)(E). Additional information is available in the ISPAD Clinical Practice Guidelines on complications. (72). Dyslipidemia, hypertension and albuminuria are more common in type 2 diabetes compared to type 1 diabetes and may be present at diagnosis and should be assessed after blood glucose control has been optimized. Confirmed hypertension (BP> 95% for age, gender and height) or albuminuria should be treated with an ACE inhibitor or, if not tolerated, an angiotensin receptor blocker (E). Combination therapy may be required if hypertension or albuminuria does not normalize on single agent treatment (E). Side effects are cough, hyperkalemia, headache and impotence (73). In addition, major congenital malformations have been reported with first trimester exposure to ACE inhibitors but not with other antihypertensive agents in non-diabetic women (74). Testing for dyslipidemia should be performed soon after diagnosis when BG control has been achieved and annually thereafter. (60,61) E Goal is LDL-C < 2.6 mmol (100 mg/dl) (68). If LDL-C is borderline (2.6-3.4 mmol;100–129 mg/ dl), or elevated (≥ 3.4 mmol; 130 mg/dl), repeat lipid profile should be performed in 6 months and dietary intervention to decrease total and saturated fat initiated. If LDL-C remains elevated after 3-6 months of attempting to optimize blood glucose control and diet, pharmacotherapy is warranted (72). Statin therapy has been shown to be safe and effective in children as in adults and should be the first pharmacologic intervention (72) although long term safety data are not available. Special attention should be paid to symptoms associated with muscles and connective tissues, as there is an increased risk of rhabdomyolysis The of T2DM in children and adolescents has required that with the of T1DM in children and adolescents the between the treatment of these T1DM is throughout the population to T2DM in North and Europe those with e.g. levels, less less well This has not been described for Asian T2DM. age. T1DM occurs throughout childhood, when is T2DM occurs in when family of families with a with T1DM have family with the disease, while 75% or more of families of the with T2DM have such The of these family to control weight and is with complications in the family and a of and in the treatment In most T1DM, beyond insulin and glucose is only for those individuals who are overweight and In all youth with T2DM, the is on and on glucose and effects of have the of T1DM and blood glucose insulin In in with an that dense increasingly and have to the of T2DM in children and its in of of including hypertension, dyslipidemia, and in the of complications may require more control in insulin T2DM than in T1DM, and attention to as by the Diabetes (21). also the ISPAD Clinical Practice Guidelines for diabetes and family for youth with type 2 diabetes is as important as it is in type 1 diabetes. and for T2DM will on and in insulin therapy and may not be required in T2DM will a greater on dietary and physical activity than is required for T1DM. should be given by with and of the and of youth with T2DM should be in a and age Because the of youth with T2DM are the ISPAD Guidelines for are to the of youth and families with T2DM The family will need to the of treatment of T2DM and to the of the required to T2DM should that the in the diagnosis type 1 type in a minority of patients can be and for the youth and The can be by the of blood glucose metabolism using therapy is to the metabolic of the specific of the of diabetes. is the of treatment of T2DM The family and should the of obesity and T2DM. must have an of the health and of the to an effective should be made in small and with the that these need to be The patient and family should be to monitor the and of and physical in any a and is for The and treatment for T2DM should include a and/or to a with and in of children with is should be to family and should be to all The family should be to dietary with including for weight reduced total and saturated fat increased and increased physical activity specific dietary are given in the ISPAD Guidelines for dietary should include: on and in of these and and for can result in substantial weight and is one of the most important for weight loss. and for the family and for the patient in an age including about dietary and activity related to and activity by of and using for that should be on in one with other activity as a family and should be in a or and not from a or of high density and in the the of and control of positive of or weight reduction in high and for and activity as for of and activity and for and should be for each patient and family that are to family and and should be to all A family or should be identified who is available to in physical activity with the may be to patients and family members. to with the dietary and is important to the of the should include: and an daily is to the of increased at reducing such as the and the time in related may be the most effective activity to be as a This should include daily to be more such as using of or to and to and and (E). for to and physical activity, including increases in daily (E). of blood glucose should be performed of should be and include a of fasting and postprandial glucose have been fasting a and daily post after the are while the within the (E). If the impaired glucose tolerance more frequent testing should be for of acute illness or when symptoms of or patients should more frequent testing and be in with their diabetes for (E). Patients on insulin or need to monitor for asymptomatic (E). should be at a year and if insulin is being used or metabolic control is should be continued in addition to pharmacologic therapy The of pharmacologic therapy is to decrease insulin resistance, increase insulin or to postprandial glucose The first used should be It has the over of reduction in without the risk of weight is decreased or remains and LDL-C and levels decrease during for type 2 diabetes in children and adolescents. of with over 3 months the need to a or insulin or in with a or a inhibitor Patients for should be on the effects of diabetes and oral agents on and oral agent should be used during pregnancy.

Background Given that early-onset type 2 diabetes mellitus (T2DM), metabolic syndrome, and hyperuricemia have been shown to have strong genetic components, statistical power of a genetic association study may be increased by focusing on early-onset subjects with these conditions. Although genome-wide association studies have identified various genes and loci significantly associated with T2DM, metabolic syndrome, and hyperuricemia, genetic variants that contribute to predisposition to these conditions in Japanese individuals remain to be identified definitively. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to early-onset T2DM, metabolic syndrome, or hyperuricemia in Japanese. We have now performed exome-wide association studies (EWASs) for early-onset subjects with T2DM, metabolic syndrome, or hyperuricemia and corresponding controls. Methods A total of 8102 individuals aged ≤65 years was enrolled in the study. The EWAS for T2DM was performed with 7407 subjects (1696 cases, 5711 controls), that for metabolic syndrome with 4215 subjects (2296 cases, 1919 controls), and that for hyperuricemia with 7919 subjects (1365 cases, 6554 controls). Single nucleotide polymorphisms (SNPs) were genotyped with Illumina Human Exome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 31,210, 31,521, or 31,142 SNPs that passed quality control to T2DM, metabolic syndrome, or hyperuricemia, respectively, was examined with Fisher's exact test. To compensate for multiple comparisons of genotypes with T2DM, metabolic syndrome, or hyperuricemia, we applied Bonferroni's correction for statistical significance of association. Results The EWAS of allele frequencies revealed that four, six, or nine SNPs were significantly associated with T2DM (P&lt;1.60 × 10–6), metabolic syndrome (P&lt;1.59 × 10–6), or hyperuricemia (P&lt;1.61 × 10–6), respectively. Multivariable logistic regression analysis with adjustment for age and sex revealed that three, six, or nine SNPs were significantly related to T2DM (P&lt;0.0031), metabolic syndrome (P&lt;0.0021), or hyperuricemia (P&lt;0.0014). After examination of the association of identified SNPs to T2DM-, metabolic syndrome-, or hyperuricemia-related traits, linkage disequilibrium of the SNPs, and results of previous genome-wide association studies, we have newly identified ZNF860 and OR4F6 as susceptibility loci for T2DM, OR52E4 and OR4F6 for metabolic syndrome, and HERPUD2 for hyperuricemia. Conclusion Given that OR4F6 was significantly associated with both T2DM and metabolic syndrome, we thus newly identified four genes (ZNF860, OR4F6, OR52E4, HERPUD2) that confer susceptibility to early-onset T2DM, metabolic syndrome, or hyperuricemia. Determination of genotypes for the SNPs in these genes may prove informative for assessment of the genetic risk for T2DM, metabolic syndrome, or hyperuricemia in Japanese.

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.

Objective To study clinical characteristics of type 2 diabetic(T2D)patients with metabolic syndrome(MS)and its components in Beijing urban communities.Methods Totally,3295 T2D patients involved in a combined prospective diabetic management study from 15 urban communities in Beijing were classified as four groups, according to 2004 Chinese Diabetes Society's definition of MS, i. e, isolated T2D, T2D with one component of MS, T2D with two components of MS and T2D with three components of MS. Their clinical characteristics were analyzed. Results ( 1 ) Among 3295 T2D patients, 155 (4. 7% )were isolated T2D, 107 (32.6%) T2D with one component of MS, 1386 (42.1%) T2D with two components of MS and 679 (20.6%) T2D with three components of MS, with an overall 62.7% (2065/3295) of T2D patients complicated with MS. (2) In these T2D patients, the more components of MS they had, the higher body mass index (BMI), waist circumference, waist to hip circumference ratio (WHR),systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting serum levels of insulin and triglyceride (TG) and the lower level of high-density lipoprotein-cholesterol (HDL) were presented (P <0. 01 ). (3) Percentage of isolated T2D in women increased from 49. 0% (76/155) to 61.9% (420/679)of those with three components of MS ( P < 0 01 ), with increasing of components of MS. (4) Multiple logistic regression analysis showed that BMI, history of hypertension, decreased HDL, increased TG,increased blood pressure, all were risk factors for T2D patients complicated with MS. Conclusions Among T2D patients in urban communities of Beijing, 95.3% (3140/3295) of them complicated with one or more components of MS, and 61.9% (420/679) of them complicated with MS. So, community diabetic management must be implemented in an all-round way, including control of blood pressure, blood lipids,body weight and so on, in addition to control of blood sugar. Key words: Community; Diabetes, type 2; Metabolic syndrome

Objective. Adiponectin is known to be decreased in insulin resistance (IR) and metabolic syndrome (MS) which can be present in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between adiponectin level, MS, and insulin sensitivity in T1DM. Research Design and Methods. The study included 77 T1DM patients divided into two groups based on the total plasma adiponectin median value. Insulin sensitivity was calculated with the equation for eGDR, and MS was defined according to International Diabetes Federation criteria. Results. Patients with higher adiponectin level (n = 39) had significantly lower waist circumference (P < 0.002), fasting venous glucose levels (P < 0.001), higher HDL3-cholesterol (P = 0.011), and eGDR (P = 0.003) in comparison to the group with lower adiponectin who showed higher prevalence of MS (P = 0.045). eGDR increased for 1.09 mg/kg−1 min−1 by each increase of 1 µg/mL total fasting plasma adiponectin (P = 0.003). In the logistic regression model, adiponectin was inversely associated with the presence of MS (P = 0.014). Conclusion. Higher adiponectin concentration is associated with lower prevalence of MS in T1DM. Whether higher adiponectin concentration has a protective role in the development of the MS in T1DM needs to be clarified in future follow-up studies.

BackgroundThe prevalence and incidence of type 1 diabetes mellitus (T1DM) in all age groups and the prevalence of metabolic syndrome in patients with T1DM in Korea were estimated.MethodsThe incidence and prevalence of T1DM between 2007 and 2013 were calculated using the Korean National Health Insurance Service (NHIS) datasets of claims. Clinical characteristics and prevalence of metabolic syndrome in individuals with T1DM between 2009 and 2013 were determined using the database of NHIS preventive health checkups.ResultsThe prevalence of T1DM in Korea between 2007 and 2013 was 0.041% to 0.047%. The annual incidence rate of T1DM in Korea in 2007 to 2013 was 2.73 to 5.02/100,000 people. Although the incidence rate of typical T1DM was highest in teenagers, it remained steady in adults over 30 years of age. In contrast, the incidence rate of atypical T1DM in 2013 was higher in people aged 40 years or older than in younger age groups. Age- and sex-adjusted prevalence of metabolic syndrome in patients with T1DM was 51.65% to 55.06% between 2009 and 2013.ConclusionT1DM may be more common in Korean adults than previously believed. Metabolic syndrome may be a frequent finding in individuals with T1DM in Korea.

Background : Non-alcoholic fatty liver disease (NAFLD) is a liver disorder commonly found in the majority of patients with metabolic risk factors, such as obesity and type 2 diabetes. Apolipoprotein B (apoB) is the moiety of low density lipoprotein (LDL) and clinical interest that provides a relative accurate estimation of circulating LDL particle. The aim of this study was to know the relationship between apoB level and occurrence of fatty liver in type 2 diabetes mellitus (DM) with metabolic syndrome. Method: A cross sectional study was conducted in patients suffered from type 2 DM with metabolic syndrome at Internal Medicine Outpatient Clinic in Moewardi Hospital Surakarta between April and May 2011. Thirty two patients with type 2 DM and metabolic syndrome were enrolled to this study and categorized into two groups; consisting of 16 patients with fatty liver and 16 patients without fatty liver. Student t-test was used in the analysis of this study. Results : Of 32 patients who fulfilled this study criteria, patients type 2 diabetes mellitus and metabolic syndrome with non-alcoholic fatty liver diseases (NAFLD) had higher apoB level than patients type 2 diabetes mellitus and metabolic syndrome without NAFLD (p = 0.013). Conclusion : NAFLD group had significantly higher apoB level than without NAFLD group in type 2 DM with metabolic syndrome patients. Keywords: apolipoprotein B, non-alcoholic fatty liver disease, type 2 DM, metabolic syndrome

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Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients