[Maturity onset diabetes of the young: just think about it]. / Diabètes MODY: il faut y penser.

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with onset in patients aged less than 25 years. It is a heterogeneous disorder due to heterozygous monogenic mutations with an autosomal dominant transmission. It could represent 2 to 5% of diabetes but is often under-diagnosed. We report three different cases of MODY, two without associated abnormalities and one with renal disorder. Mutations concern genes that are directly involved in the beta-cell function. In patients with non-syndromic diabetes, more than 99% of MODY result from mutations in hepatocyte nuclear factor-1-alpha (HNF-1-alpha ; formerly MODY 3), glucokinase (MODY 2), or HNF-4-alpha (MODY 1). The symptoms manifest slowly with the absence of obesity and ketosis in most cases. MODY is usually treated by diet, oral diabetes medications or insulin. Treatment and prognosis vary depending on the genetic mutation. Clinicians should keep in mind the possibility of MODY, especially in antibody-negative youth with familial diabetes. Making a diagnosis of MODY may have important implications for the guidance of appropriate treatment, prognosis and genetic counselling.

Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen.

[Evaluation of DCA vantage for rapid in-clinic measurement of HbA1c on capillary blood in young type 1 diabetic patients]. / Evaluation du DCA Vantage pour une mesure rapide de l'HbA1c au cabinet sur sang capillaire chez des jeunes patients diabétiques de type 1.

Rapid in clinic measurement of glycated hemoglogin (HbA1c) allows to determine the level of metabolic control within a few minutes on capillary blood. We have evaluated the new DCA Vantage (Siemens) based on an immunological technique, replacing the DCA 2000+ (Siemens). The study included 120 unselected young type 1 diabetic patients, with different degrees of metabolic control. The DCA Vantage was compared with the HPLC system (Menarini HA 8160) whose deviation from the DCCT was < 0.1% across the clinical range. The mean underestimation of the DCA Vantage was -0.40%. The agreement limits (+/- 1.96 SD) were between 0.14% and -0.93%; this means +/- 0.53% around -0.40%. In conclusion, the DCA Vantage underestimates HbA1c levels; however it met the acceptance criteria of having a coefficient of variation < 3%.

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients.

In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA(+) , GADA(+) , IA-2A(+) and/or ZnT8A(+) relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and 20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age-independent in IA-2A(+) and/or ZnT8A(+) relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for ≥ 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.

Care delivery and outcomes among Belgian children and adolescents with type 1 diabetes.

UNLABELLED: We aimed to investigate care processes and outcomes among children and adolescents with type 1 diabetes treated in hospital-based multidisciplinary paediatric diabetes centres. Our retrospective cross-sectional study among 12 Belgian centres included data from 974 patients with type 1 diabetes, aged 0-18 years. Questionnaires were used to collect data on demographic and clinical characteristics, as well as process of care completion and outcomes of care in 2008. Most patients lived with both biological or adoption parents (77 %) and had at least one parent of Belgian origin (78 %). Nearly all patients (≥95 %) underwent determination of HbA(1c) and BMI. Screening for retinopathy (55 %) and microalbuminuria (73 %) was less frequent, but rates increased with age and diabetes duration. Median HbA(1c) was 61 mmol/mol (7.7 %) [interquartile range 54-68 mmol/mol (7.1-8.4 %)] and increased with age and insulin dose. HbA(1c) was higher among patients on insulin pump therapy. Median HbA(1c) significantly differed between centres [from 56 mmol/mol (7.3 %) to 66 mmol/mol (8.2 %)]. Incidence of severe hypoglycaemia was 30 per 100 patient-years. Admissions for ketoacidosis had a rate of 3.2 per 100 patient-years. Patients not living with both biological or adoption parents had higher HbA(1c) and more admissions for ketoacidosis. Parents' country of origin was not associated with processes and outcomes of care. CONCLUSION: Outcomes of care ranked well compared to other European countries, while complication screening rates were intermediate. The observed centre variation in HbA(1c) remained unexplained. Outcomes were associated with family structure, highlighting the continuing need for strategies to cope with this emerging challenge.

Risk markers for cardiovascular disease in young type 1 diabetic patients: lipoproteins, high-sensitivity C-reactive protein and adiponectin.

OBJECTIVES: Lipoproteins, high-sensitivity C-reactive protein (hs-CRP) and adiponectin have been studied as risk factors for cardiovascular disease (CVD). The aim of this study was to measure and analyze those risk markers in young type 1 diabetic patients and to evaluate the association between adiponectin and different parameters. METHODS: This cross-sectional study analyzed body mass index, subscapular skinfold thickness, physical activity, nutrition, glycated haemoglobin (HbA1c), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, hs-CRP and adiponectin in 148 young type 1 diabetic patients [age--median (interquartile range)--13.5 (10.3-16.0) yr]. Linear and multiple regression analysis were used. RESULTS: Median HbA1c was 7.5 (7.0-8.1)%. Median cholesterol and hs-CRP levels were normal. Adiponectin was 14.9 (10.8-19.0) microg/ml. There was no correlation between adiponectin and age, diabetes duration, body mass index, physical activity, protein, fat or carbohydrate intake, HbA1c, serum lipids or hs-CRP. But there was a negative correlation between serum adiponectin and skinfold thickness and a positive correlation between adiponectin and daily energy intake. Multiple linear regression analysis showed an independent positive correlation with daily energy intake, saturated fat intake and apolipoprotein B levels. CONCLUSIONS: In children and adolescents with relatively well controlled glycaemia, there are no abnormalities of risk markers for cardiovascular disease: lipoproteins, hs-CRP and adiponectin. Adiponectin levels are associated with daily energy intake, saturated fat intake and apolipoprotein B levels suggesting that increased levels of adiponectin could protect patients at increased risk of CVD. A longitudinal analysis is needed to follow up these factors and any occurrence of cardiovascular disease.

Alexithymia is associated with glycaemic control of children with type 1 diabetes.

AIM: This study examined the respective contributions of the demographics, medical variables and alexithymia characteristics of young diabetics to their glycaemic control. The goal was to replicate the role of the 'difficulty describing feelings' factor of alexithymia in the prediction of poor glycaemic control as has been found in adult diabetic populations. METHOD: The study included 45 type 1 diabetic children, aged 8-12 years (24 girls and 21 boys). Participants completed a sociodemographic questionnaire and provided medical information on their diabetes. HbA(1c) values (glycated haemoglobin), and the number of severe hypoglycaemic episodes and hospitalizations for hyperglycaemia, were collected for the previous 12 months (3 months for severe hypoglycaemias). Alexithymia characteristics were measured by means of the Alexithymia Questionnaire for children. RESULTS: Hierarchical regression analyses confirmed that both demographic (marital status and parental education; P<0.05) and medical (duration of diabetes and daily self-monitoring of blood glucose frequency; P<0.01) variables are associated with HbA(1c) levels. More important, one alexithymia factor (difficulty describing feelings) was found to be an additional predictor over and above the other variables (P<0.01), explaining an additional 12% of the total variance in HbA(1c) levels. CONCLUSION: Confirming results already observed in diabetic adults, the present findings show, for the first time, that children who have difficulties in expressing their feelings to others are more at risk of poor glycaemic control. In future, it will be useful to identify the diabetic young people who have such difficulties and to consider interventions designed specifically for them.

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.

Does family cohesiveness and parental alexithymia predict glycaemic control in children and adolescents with diabetes?

AIM: Several studies indicate that family functioning and parental expressiveness can influence children's glycaemic control. However, previous studies have had contradictory findings. Furthermore, no previous work has simultaneously explored the mother's and father's perception of family cohesiveness together with maternal and paternal alexithymia in relation to a child's diabetic control. In this study, we examined whether the parental perception of family cohesion and the parents' degree of alexithymia could predict their child's or adolescent's glycaemic control (severe hypoglycaemia, hospitalizations for hyperglycaemia and HbA(1c)) after adjusting for demographic variables. METHODS: The study included 45 Belgian families with at least one type 1 diabetic child aged six to 18 years (25 girls and 20 boys). Parents completed demographic questionnaires about themselves and their children. Information on type 1 diabetes in their child and the family-medical history were also collected. The number of severe-hypoglycaemic events and hospitalizations for hyperglycaemia were documented for the last 12 months, as were HbA(1c) levels over the last 16 months. Finally, family cohesiveness (FACES-III) and parental alexithymia (TAS-20) were assessed. RESULTS: Hierarchical regression analyses showed that the perception of family cohesion by mothers (P<0.05) was a predictor of the number of severe hypoglycaemic events in the last 12 months. Parents' demographic variables (marital and professional status, P<0.001) and maternal alexithymia (P<0.05) were found to be predictors of the number of hospitalizations for hyperglycaemia in the last 12 months. As for HbA(1c), only two parental demographic variables were significant predictors (marital and professional status, P<0.01 and P<0.05, respectively). CONCLUSION: The maternal perception of family cohesiveness and maternal alexithymia predict on glycaemic control in children and adolescents with diabetes.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.

[Rational use of insulin analogues in the treatment of type 1 diabetic children and adolescents: personal experience]. / Utilisation rationnelle des nouveaux analogues de l'insuline dans le traitement du diabète de type 1 chez les enfants et adolescents: expérience personnelle.

In the last decade, four fast- and long-acting insulin analogues have been created. Due to the pharmacokinetic characteristics of insulin analogues, they provide an insulin profile closer to normal physiology than can be achieved with human insulins. However, they do not necessarily improve glycated haemoglobin, but they allow better quality of life. In the two daily insulin injection regime, fast-acting analogues are very useful to rapidly correct hyperglycaemia, to allow sleeping in and eating something sweet. In the basal-bolus regime (> or =4 insulin injections), long-acting analogues reduce nocturnal hypoglycaemias and improve fasting blood glucose. In the two insulin regime (2 or > or =4 injections), rapid-acting human insulin must not be systematically replaced by a fast-acting analogue. On the other hand, insulin dose alteration must be triple: retrospective, according to numerous previous experiments, in order to enjoy more freedom for meals, sports, etc.; prospective according to programmed changes in meals and sports; with only a "touch" of compensatory adaptation according to actual glycaemia.

[Insulin analogues: place of detemir (Levemir)]. / Les analogues de l'insuline: la place de la détémir (Levemir).

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50 %). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.

Insulin-dependent diabetes mellitus as long term complication of haemolytic-uraemic syndrome.

Haemolytic-uraemic syndrome (HUS) is a rare cause of insulin-dependent diabetes mellitus during the acute stage. We previously reported the case of a 3-year-old girl having presented with typical HUS with diarrhea, microangiopathic anaemia, thrombocytopenia and acute renal failure (17 days of anuria). Transient hyperglycaemia (highest level: 513 mg/dl) was observed, requiring continuous intravenous insulin infusion for 9 days. Subcutaneous insulin injections were stopped after 24 days. Oral glucose tolerance test performed 4 months after normalization of blood glucose was normal. HLA DQ genotype (DQA1-DQB1.AZH/DQA3-DQB3.1) was not at risk for type 1 diabetes and there were no auto-antibodies (ICA and IAA). The 3-years follow-up was marked by persistent arterial hypertension, proteinuria and slight renal insufficiency despite angiotensin-converting enzyme inhibitor treatment. Ten years after HUS occurred (the patient had been lost to follow-up for 7 years), she came back with complaints of headache but neither polyurodipsia nor weight loss. She was found to have arterial hypertension. Chronic renal impairment had moderately progressed with decreased glomerular filtration rate (63 ml/min/1.73 m2) and proteinuria (2 g/24 hours). Fasting blood glucose was 189 mg/dl and reached 315 mg/dl during an oral glucose tolerance test. HbA1c level was 8.2% (N<6.2%) and diabetes mellitus was diagnosed without any signs of autoimmunity (IAA, ICA, GADA and IA2B were negative). Good glycaemic control was obtained with 0.5 U/kg/day of insulin. In conclusion, transient beta-cell dysfunction complicating HUS acute stage may evolve to overt non-autoimmune diabetes mellitus (microangiopathic process?), even after a long free interval. This case emphasizes the need for a long-term follow-up of patients with HUS.

[Insulin analogues: place of detemir (levemir)]. / Les analogues de l'insuline: la place de la détémir (levemir).

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/ kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover the meals, may be done with a rapid acting human insulin and/or a fast acting analogue. In comparison with NPH insulin, detemir has been shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50%). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.

Sex- and season-dependent differences in C-peptide levels at diagnosis of immune-mediated type 1 diabetes.

AIMS/HYPOTHESIS: The incidence of type 1 diabetes varies according to age, sex and season of diagnosis. We investigated whether these and other clinical, biological and anthropometric parameters were correlated with residual beta cell function in newly diagnosed patients, since it is possible that the nature of external and/or genetic disease accelerators may be (partly) reflected in the inaugural disease presentation. MATERIALS AND METHODS: The correlates of random C-peptide levels sampled shortly after diagnosis (median [interquartile range]: 3 [0-14] days) were studied by multivariate analysis in 1,883 islet-antibody-positive diabetic patients aged <40 years who were diagnosed between 1989 and 2000. RESULTS: Higher C-peptide levels (above percentile 50 of patients) were associated with older age at diagnosis, female sex, diagnosis in the high-incidence season (October to March), less-decreased BMI (expressed as a standard deviation score), lower insulin requirements after stabilisation, lower prevalence of ketonuria and a less-increased glycaemia at diagnosis (all p < 0.001). C-peptide levels were not correlated with calendar year at diagnosis, duration of symptoms prior to diagnosis, HLA-DQ2/DQ8 genotype or islet antibody status. CONCLUSIONS/INTERPRETATION: Sex- and season-dependent differences in residual functional beta cell mass and/or insulin resistance have been identified at diagnosis of type 1 diabetes. They may reflect differences in disease-precipitating external or lifestyle factors and should be further investigated longitudinally in prediabetes to further identify putative aetiological factors, which may provide targets for prevention.

[What glycemic control can be achieved in diabetic children and adolescents to avoid complications? Personal experience]. / Quel contrôle glycémique peut être obtenu chez les enfants et adolescents diabétiques pour éviter les complications? Expérience personnelle.

The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications by maintaining blood glucose concentrations close to the normal range and an HbA1c level under 7%. The number of daily insulin injections, 2 or > or =4 or pumps, by itself does not necessarily give better results, but the 4-injection regimen allows greater freedom, taking into account that the proper insulin adjustment is difficult before adolescence. Successful glycaemic control in young patients depends mainly on the quality and intensity of diabetes education. Any dogmatism must be avoided. Dietary recommendations issued over the last few years are the same for diabetic and nondiabetic individuals in order to avoid degenerative diseases. In the twice-daily injection regimen, the allocation of carbohydrates throughout the day is essential. Due to their pharmakokinetic characteristics, fast-acting and long-acting insulin analogues have specific indications in both the twice-daily injection regimen and the basal-bolus insulin therapy. They improve quality of life, without necessarily reducing HbA1c. In the two daily insulin injection regimen, fast-acting analogues are very useful to rapidly correct hyperglycaemia, to allow sleeping in and eating something sweet. In the basal-bolus regimen, long-acting analogues reduce nocturnal hypoglycaemias and improve fasting blood glucose. Clinical studies, conducted since the 1970s by our team, have demonstrated that screening for subclinical retinopathy (fluorescein angiography), neuropathy (conduction velocities), nephropathy (microalbuminuria), should be started at puberty and at least 3 years after the diagnosis of diabetes. The goal is to detect early abnormalities responsible for subclinical disorders that can be reversed by improved metabolic control, thus preventing the occurrence of irreversible potentially incapacitating lesions. This motivates both the patient and the doctor in order to obtain good HbAlc levels. The mean HbAlc levels of our diabetic children and adolescents are among the lowest in the review of literature and in the international comparisons by the Hvidøre Study Group on Childhood Diabetes.

[Weight of obesity in (pre)type 2 diabetes in children and adolescents: how and when to screen for?]. / Le poids de l'obésité dans le (pré)diabète de type 2 chez les enfants et adolescents : quand et comment le rechercher ?

There has been wide recognition in the past decade of the increasing frequency of type 2 diabetes in youth, largely but not exclusively in North America. In some American locations and populations, incidence and prevalence of type 2 diabetes are much higher than those of type 1 diabetes, because of increased calorie and fat intake, and decreased exercise. The increasing prevalence of type 2 diabetes in the United States has closely paralleled the increase in childhood obesity noted there, but now across the Western world. Besides obesity, the other youth risk factors for type 2 diabetes are: ethnicity, puberty, family history, metabolic syndrome, polycystic ovary syndrome, acanthosis nigricans. Any feature or condition associated with insulin resistance/hyperinsulinemia should alert to screen youth at increased risk for (pre)type 2 diabetes. Treatment goals are to decrease weight and increase exercise, to normalize insulinemia, glycemia and HbA1c, to control hypertension and hyperlipidemia. The aim of the pharmacological therapy is to decrease insulin resistance, namely by metformin. Sometimes, insulin therapy is necessary.