Tissue-specific glucose partitioning and fat content in prediabetes and type 2 diabetes: whole-body PET/MRI during hyperinsulinemia.

OBJECTIVE: To obtain direct quantifications of glucose turnover, volumes and fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated approach for whole-body imaging. DESIGN AND METHODS: Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI. RESULTS: Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in controls to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to control subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity assessed as glucose infusion rate correlated with liver MRglu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MRglu only in the same muscle group. CONCLUSIONS: This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.

Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort.

OBJECTIVE: Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity. RESEARCH DESIGN AND METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. RESULTS: Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA1c were not associated with BGU. CONCLUSIONS: In this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU.

Hipoglucemia por hiperinsulinismo endógeno / Endogenous hyperinsulinism hypoglycemia

RESUMEN La hipoglucemia por hiperinsulinismo endógeno constituye un reto terapéutico. Se describen las características clínicas, bioquímicas e imagenológicas de pacientes con diagnóstico de hiperinsulinismo endógeno atendidos en el Instituto Nacional de Endocrinología en el periodo 2004-2018(AU)

ABSTRACT Hypoglycemia due to endogenous hyperinsulinism constitutes a therapeutic challenge. The clinical, biochemical and imaging characteristics of patients diagnosed with endogenous hyperinsulinism treated at the National Endocrinology Institute from 2004 to 2018 are described(AU)

Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults.

BACKGROUND: There is growing evidence to suggest that the brain is an important target for insulin action, and that states of insulin resistance may extend to the CNS with detrimental effects on cognitive functioning. Although the effect of systemic insulin resistance on peripheral organs is well-studied, the degree to which insulin impacts brain function in vivo remains unclear. METHODS: This randomized, single-blinded, 2-way-crossover, sham-controlled, pilot study determined the effects of hyperinsulinemia on fMRI brain activation during a 2-back working memory task in 9 healthy older adults (aged 57-79 years). Each participant underwent two clamp procedures (an insulin infusion and a saline placebo infusion, with normoglycemia maintained during both conditions), to examine the effects of hyperinsulinemia on task performance and associated blood-oxygen-level dependent (BOLD) signal using fMRI. RESULTS: Hyperinsulinemia (compared to saline control) was associated with an increase in both the spatial extent and relative strength of task-related BOLD signal during the 2-back task. Further, the degree of increased task-related activation in select brain regions correlated with greater systemic insulin sensitivity, as well as decreased reaction times and performance accuracy between experimental conditions. CONCLUSION: Together, these findings provide evidence of insulin action in the CNS among older adults during periods of sustained cognitive demand, with the greatest effects noted for individuals with highest systemic insulin sensitivity. FUNDING: This work was funded by the National Institutes of Health (5R21AG051958, 2016).

68Ga DOTA-Exendin PET/CT for Detection of Insulinoma in a Patient With Persistent Hyperinsulinemic Hypoglycemia.

Insulinomas are the most common functioning pancreatic neuroendocrine tumors and the leading cause of persistent hypoglycemia with hyperinsulinemia in adults. Glucagon-like-peptide-1 (GLP) receptor analogs are the latest agents being used in the detection of insulinomas, with initial reports suggesting high sensitivity due to universal GLP1 receptor expression on these tumors. PET/CT imaging in this patient using Ga DOTA-Exendin, a GLP receptor analog, proved useful for accurate localization of the culprit lesion, aiding in the definitive management of the patient.

Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.

Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.

Role of (68)Ga somatostatin receptor PET/CT in the detection of endogenous hyperinsulinaemic focus: an explorative study.

PURPOSE: To explore the role of (68)Ga-DOTATATE/DOTATOC PET/CT (SR PET/CT) in patients with suspicion of or histopathologically proven pancreatogenic hyperinsulinaemic hypoglycaemia. METHODS: We included 13 patients with histopathologically proven or a high clinical suspicion of pancreatogenic hyperinsulinaemia. All the patients underwent a SR PET/CT scan. The results were correlated with histopathological findings. Normalization of blood glucose levels after resection of the pancreatic lesion, as well as a cytological and/or pathological diagnosis of insulinoma, was considered the diagnostic gold standard for insulinoma. The diagnosis of nesidioblastosis was based on exclusion of an insulinoma and conclusive pathological examination of a segment of the pancreas. Malignant insulinoma was defined as the presence of locoregional or distant metastases. RESULTS: Based on histopathology, 13 patients were found to have pancreatic hyperinsulinaemia: two patients had malignant insulinoma, eight had nonmetastasized insulinoma, and three had nesidioblastosis. SR PET was positive in 11 of the 13 patients (84.6 %) with a final diagnosis of endogenous pancreatic hypoglycaemia. Histopathological staining confirmed 16 foci of hyperinsulinism (insulin positivity). SR PET detected 14 of the 16 lesions, resulting in a sensitivity of 87 %. One intrapancreatic spleen was falsely diagnosed as insulinoma focus on SR PET, resulting in positive predictive value of 93.3 %. Immunohistochemical staining of somatostatin receptor (SSR) subtype 2a was available in ten specimens: two nesidioblastosis, and seven benign and one malignant insulinoma. Eight out of the ten specimens (80 %) stained strongly to moderately positive. Seven of the eight SSR2a-positive lesions were picked up on SR PET. Based on the results of SR PET/CT, nine patients achieved complete remission of the hypoglycaemic events during follow-up. CONCLUSION: This explorative study suggests that SR PET in combination with CT may play a significant role in the detection and management of patients with pancreatogenic hyperinsulinaemic hypoglycaemia. A large proportion of insulinomas express SSR2a, and a larger study is needed to fully assess the diagnostic accuracy of SR PET in patients with insulinoma and nesidioblastosis compared with current localizing studies used in clinical practice.

Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia.

Schizophrenia is a severe and chronic neuropsychiatric disorder which affects 1% of the world population. Using the brain imaging technique positron emission tomography (PET) it has been demonstrated that persons with schizophrenia have greater dopamine transmission in the striatum compared to healthy controls. However, little progress has been made as to elucidating other biological mechanisms which may account for this hyperdopaminergic state in this disease. Studies in animals have demonstrated that insulin receptors are expressed on midbrain dopamine neurons, and that insulin from the periphery acts on these receptors to modify dopamine transmission in the striatum. This is pertinent given that several lines of evidence suggest that insulin receptor functioning may be abnormal in the brains of persons with schizophrenia. Post-mortem studies have shown that persons with schizophrenia have less than half the number of cortical insulin receptors compared to healthy persons. Moreover, these post-mortem findings are unlikely due to the effects of antipsychotic treatment; studies in cell lines and animals suggest antipsychotics enhance insulin receptor functioning. Further, hyperinsulinemia - even prior to antipsychotic use - seems to be related to less psychotic symptoms in patients with schizophrenia. Collectively, these data suggest that midbrain insulin receptor functioning may be abnormal in persons with schizophrenia, resulting in reduced insulin-mediated regulation of dopamine transmission in the striatum. Such a deficit may account for the hyperdopaminergic state observed in these patients and would help guide the development of novel treatment strategies. We hypothesize that, (i) insulin receptor expression and/or function is reduced in midbrain dopamine neurons in persons with schizophrenia, (ii) basal insulin should reduce dopaminergic transmission in the striatum via these receptors, and (iii) this modulation of dopaminergic transmission by basal insulin is reduced in the brains of persons with schizophrenia.

Postprandial hyperinsulinaemic hypoglycaemia secondary to a congenital portosystemic shunt.

BACKGROUND: Portosystemic shunts (PSS) are abnormal vascular connections between the portal vein or its tributaries and the systemic vein that allow mesenteric blood to reach the systemic circulation without first passing through the liver. PSS can be associated with various syndromes and can lead to serious complications. We report a rare case of a child with PSS and recurrent hypoglycaemia. CASE: A 20-month-old girl with Down's syndrome presented with recurrent hypoglycaemic episodes. She had multiple anomalies including a ventricular septal defect, oesophageal atresia and tracheo-esophageal fistula, gastro-oesophageal reflux, and conjugated hyperbilirubinaemia. The initial investigations suggested hyperinsulinaemic hypoglycaemia (HH). She did not respond to diazoxide. An oral glucose tolerance test suggested postprandial HH. Further vascular imaging showed a side-to-side portocaval shunt (Abernethy malformation) with relative hypoperfusion of the liver. Hypoglycaemia resolved following surgical closure of the portocaval shunt. CONCLUSION: PSS can rarely be associated with HH, possibly due to lack of insulin degradation in the liver. Surgical closure of the shunt resolves the hypoglycaemia.

18F-FDOPA PET/CT imaging of insulinoma revisited.

PURPOSE: (18)F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to (18)F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with (18)F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. METHODS: A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using (18)F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after (18)F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after (18)F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. RESULTS: In the study group, (18)F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All (18)F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted (18)F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final diagnosis was benign insulinoma in four, nesidioblastosis in one, and no definitive diagnosis in the remainder. (18)F-FDOPA PET/CT failed to detect any tumour in these patients. CONCLUSION: According to our experience, CD administration before (18)F-FDOPA injection leads to low residual pancreatic (18)F-FDOPA activity preserving tumoral uptake with consequent insulinoma detection in more than half of adult patients with HH and more than 70 % of patients with a final diagnosis of insulinoma. If (18)F-FDOPA PET/CT is indicated, we strongly recommend combining CD premedication with early acquisition centred over the pancreas.

Dynamic 18F-FDOPA PET Findings After Carbidopa Premedication in 2 Adult Patients With Insulinoma-Related Hyperinsulinemic Hypoglycemia.

(18)F-fluorodihydroxyphenylalanine (FDOPA) PET seems to be of limited value to localize pancreatic insulin-secreting tumors in adult with hyperinsulinemic hypoglycemia. Carbidopa is an efficient inhibitor of the peripheral aromatic amino acid decarboxylase, significantly reducing the physiological pancreatic FDOPA uptake. Nevertheless, carbidopa effect on FDOPA uptake in insulinomas is not fully elucidated. No final consensus has been reached about the usefulness of carbidopa in patients with insulinoma-related hyperinsulinemic hypoglycemia. Moreover, the ideal timing for PET/CT acquisitions is a matter of discussion. We report the results of dynamic FDOPA PET performed after carbidopa premedication in 2 adult patients with insulinoma.

Effect of insulin resistance associated with compensatory hyperinsulinemia on the long-term prognosis in patients with vasospastic angina.

BACKGROUND: Insulin resistance associated with compensatory hyperinsulinemia plays a significant role in the pathogenesis of cardiovascular diseases, including vasospastic angina (VSA). However, the effects of insulin resistance associated with hyperinsulinemia on the long-term prognosis in patients with VSA remain unclear. METHODS: A total of 265 selected patients with VSA and 56 control subjects with atypical chest pain were enrolled in the present study. Patients with VSA had a positive acetylcholine (ACh) provocation test with normal coronary angiograms, and control subjects had a negative ACh test and normal coronary angiograms. A 75-g oral glucose tolerance test was performed, and the plasma glucose and immunoreactive insulin (IRI) levels were measured before, and 30 min and 120 min (IRI 120) after the 75-g glucose load. RESULTS: During the median follow-up period of 90.0 months, thirty-one patients developed cardiac events, including 6 sudden cardiac deaths and 25 readmissions for acute coronary syndrome. Cardiac events occurred in 38.9% of the patients with an IRI 120 ≥ 80 µU/ml and only 1.6% of the patients with an IRI 120<80 µU/ml (log rank 77.220, p<0.001). A multivariate analysis showed that an IRI 120 ≥ 80 µU/ml (hazard ratio 27.49, 95% confidence interval: 4.66-162.10, p<0.001) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that insulin resistance associated with compensatory hyperinsulinemia increases the risk of cardiac events in VSA patients.

[The role of hyperinsulinemia and insulin resistance in development of chronic kidney disease in patients with metabolic syndrome].

AIM: To examine relations between hyperinsulinemia, insulin resistance (IR). components of metabolic syndrome (MS) and predisposition to renal damage, MATERIAL AND METHODS: A total of 94 MS patients (64 males and 30 females, age 30-67 years, mean age 52 +/- 9 years) entered the study. The examination included measurement of waist and hip circumference, body mass index (BMI), HOMA index, estimation of lipids and immunoreactive insulin concentrations. Renal damage was assessed by glomerular filtration rate and urinary excretion of albumin. The patients were divided into groups by IR and BMI. RESULTS: A strong correlation was found between IR markers and lipid metabolism disorders, hemodynamic parameters. Statistics show that IR is an independent unfavourable factor of renal damage in MS patients. CONCLUSION: IR is an essential component of MS and an independent factor of development of chronic kidney disease in MS patients.

System approach to modeling of liver glucose metabolism with physiologically interpreted model parameters outgoing from [18F]FDG concentrations measured by PET.

New mathematical models from physiologically interpreted parameters capable of evaluating glucose metabolism within the liver and/or the whole body were developed. The group of pigs in a fasting state and the group of pigs with euglycemic supraphysiological hyperinsulinemia were scanned by positron emission tomography after a single dose of [(18)F]FDG tracer. Simultaneously frequent sampling of the dynamic data of [(18)F]FDG plasma concentration in artery, portal vein and hepatic vein was obtained. A system approach to the liver and/or the whole-body system by the tools of linear dynamic sysztem theory was used. Three kinds of structural models, single input and single output or multiple outputs and multiple inputs and single output, were identified. Differences between the group of fasting pigs and the group of pigs in euglycemic supraphysiological hyperinsulinemia were identified by estimated parameters of the structural models. The suitability of the structural mathematical models for the estimation of physiologically interpreted parameters from PET was validated.

Functional imaging in hyperinsulinemic hypoglycemia after gastric bypass surgery for morbid obesity.

CONTEXT: Hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass (RYGB) has been increasingly reported. It is induced by ß-cell hyperplasia often referred to as nesidioblastosis. Positron emission tomography (PET) with [11C]-5-hydroxytryptophan ((11)C-HTP) and 6-[18F]fluoro-3,4-dihydroxy-l-phenylalanine ((18)F-DOPA) has been successfully applied to image neuroendocrine tumors. No data are available of the usefulness of these functional imaging techniques in post-RYGB in this new endocrine disorder, neither for diagnostic purposes nor for follow-up. OBJECTIVE: We present a patient with post-RYGB hypoglycemia who underwent (11)C-HTP and (18)F-DOPA PET scintigraphy for diagnostic purposes and to evaluate the effect of additional laparoscopic adjustable banding of the pouch as a surgical therapy for this disorder. PATIENT: We describe a woman with biochemically confirmed post-RYGB hypoglycemia who showed diffuse uptake of the (11)C-HTP and (18)F-DOPA tracers in the entire pancreas. After failure of dietary and medical treatment options, she underwent a laparoscopic adjustable banding for pouch dilatation. Subjective improvement was noted, which coincided with decreased uptake of (18)F-DOPA and (11)C-HTP in the head of the pancreas. CONCLUSIONS: Functional imaging by (18)F-DOPA- and (11)C-HTP-PET can accurately visualize diffuse endocrine pancreatic activity in post-gastric bypass hyperinsulinemic hypoglycemia. Both (11)C-HTP- and (18)F-DOPA-PET imaging appear to have a similar diagnostic performance in the presented case, and uptake of both tracers potentially relates to disease activity after surgical intervention.

Fetal anterior wall thickness and amniotic fluid insulin levels: an interdependence?

PURPOSE: Excessive fetal fat as the hallmark of GDM pregnancy complications is one consequence of fetal hyperinsulinism. Noninvasive methods for fetal surveillance and measurement of fetal fat are needed. The purpose of this study was to test the hypothesis that measurements of the fetal anterior abdominal wall thickness (AAWT) in women with GDM will allow early detection of fetal hyperinsulinism. MATERIALS AND METHODS: Amniocentesis was performed between 28 and 32 weeks of gestation (wks) in 220 women with GDM (diagnosed by 75 g oGTT at 24 to 28 wks). Amniotic fluid insulin levels (AFIL) were determined by a commercially available radioimmunoassay. Transabdominal ultrasound provided fetal biometric measurements following standard procedures and the AAWT including fetal skin and subcutaneous tissue at the time of amniocentesis. Maternal parameters (weight, BMI, oGTT blood glucose levels and mean daily blood glucose levels) were correlated with fetal biometric data and with AFIL. RESULTS: There was no difference in AAWT in women with GDM and no correlation with mean AFIL. AFIL also did not correlate with any other fetal measurement or with mean oGTT blood glucose levels. AFIL only showed a correlation with maternal weight (p = 0.02) and maternal BMI (p = 0.01). The correlation was present for values both before pregnancy and at the time of amniocentesis. CONCLUSION: In the early third trimester, AAWT measurements do not correlate with fetal insulin levels.

Atrophy and intramuscular fat in specific muscles of the thigh: associated weakness and hyperinsulinemia in stroke survivors.

PURPOSE: Sarcopenia and increased fat infiltration in muscle may play a role in the functional impairment and high risk for diabetes in stroke. Our purpose was to compare muscle volume and muscle attenuation across 6 muscles of the paretic and nonparetic thigh and examine the relationships between intramuscular fat and insulin resistance and between muscle volume and strength in stroke patients. METHODS: Stroke participants (70; 39 men, 31 women) aged 40 to 84 years, BMI = 16 to 45 kg/m(2) underwent multiple thigh CT scans, total body scan by DXA (dual-energy X-ray absorptiometry), peak oxygen intake (VO(2peak)) graded treadmill test, 6-minute walk, fasting blood draws, and isokinetic strength testing. RESULTS: Muscle volume is 24% lower and subcutaneous fat volume is 5% higher in the paretic versus nonparetic thigh. Muscle attenuation (index of amount of fat infiltration in muscle) is 17% higher in the nonparetic midthigh than the paretic. The semitendinosis/semimembranosis, biceps femoris, sartorius, vastus (medialis/lateralis), and rectus femoris have lower (between 9% and 19%) muscle areas on the paretic than the nonparetic thigh. Muscle attenuation is 15% to 25% higher on the nonparetic than the paretic side for 5 of 6 muscles. The nonparetic midthigh muscle attenuation is negatively associated with insulin. Eccentric peak torque of the nonparetic leg and paretic leg are associated with the corresponding muscle volume. CONCLUSIONS: The skeletal muscle atrophy, increased fat around and within muscle, and ensuing muscular weakness observed in chronic stroke patients relates to diabetes risk and may impair functional mobility and independence.

[Doppler studies of gestational diabetes in the third trimester]. / Plazentare Widerstandsmessung bei Gestationsdiabetes im III. Trimenon.

PURPOSE: Gestational diabetes (GDM) is related to increased maternal and neonatal morbidity. Maternal hyperglycemia causes fetal hyperglycemia and consequently fetal hyperinsulinism. The impaired glucose metabolism will lead to prenatal and postnatal complications. The main issue of this study is the influence of GDM in evaluating Doppler flow measurements in the umbilical artery (UA). MATERIALS AND METHODS: Pregnancies from gestational age > 34 + 0 were included in this case control study. The study period was 18 months. The last Doppler measurement in pregnancies with GDM (diet-controlled and insulin-dependent) was compared to the healthy control group. Our collected data included the last prenatal Doppler flow recordings (resistance index (RI) in the umbilical artery (UA)). RESULTS: In women with diet-controlled GDM, a significant decrease in the RI (p = 0.002) in the UA has been observed. Insulin-treated diabetic and healthy control pregnancies showed no difference in the RI. CONCLUSION: Doppler flow examinations with RI measurements in patients with GDM differ significantly with respect to healthy controls. In insulin-treated women the RI indices are not different from the control group, while in the diet-controlled group a significant decrease was noted and additionally might show a possible maternal metabolic dysfunction.

Long-term metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome.

OBJECTIVE: The objective of this study is to determine the ability of metformin treatment in reducing the prevalence of metabolic syndrome (MS) and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome (PCOS). DESIGN: Clinical Trial. PATIENTS: We recruited 140 hyperinsulinaemic overweight women with PCOS in their reproductive age. Metformin treatment (500 mg × 3/die) was prescribed to each patient for twelve months. MEASUREMENTS: The primary outcome was to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) and MS in hyperinsulinaemic overweight patients with PCOS. The secondary outcome was to evaluate, in the same patients, the effects of metformin therapy on endocrine, metabolic and hepatic parameters. RESULTS: At basal evaluation, NAFLD was diagnosed in 81 of 140 patients with PCOS (57·85%); MS was present only in the NAFLD group (32·09%vs 0%; P < 0·001). After twelve months, metformin is able to significantly reduce, in the same group, the prevalence of MS (28·9%vs 13·5%; P < 0·01). An improvement of hepatic parameters and a significant decrease in oligomenorrhea (85·7%vs 19%, P < 0·001) were also observed. CONCLUSIONS: Treatment with metformin is indicated in all hyperinsulinaemic overweight patients with PCOS, especially in those with NAFLD. These data appear even more interesting considering their increased risk to develop metabolic and hepatic complications.