Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?

BACKGROUND: Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. MATERIALS AND METHODS: Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. RESULTS: The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44.6 +/- 4.9 vs. 60.0 +/- 4.8 micromol min(-1) kg FFM(-1), P = 0.037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180-240 min (Delta0.77 +/- 0.11 mmol L(-1)), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2.13 +/- 0.51 vs. 0.70 +/- 0.35 mmol L(-1), P = 0.03), only in the REL. CONCLUSIONS: These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver.     

Vitamin D deficiency,insulin resistance and thyroid dysfunction in obese patients: is inflammation the common link?

Abstract

The aim of this article is to study the possible relation of serum vitamin D concentrations to body mass index (BMI), visceral fat thickness (VFT), insulin resistance (IR), inflammation (serum monocyte chemoattractant protein-1 – MCP-1) and thyroid parameters in obese patients. A total of 158 non-diabetic, obese patients aged 19–68 without a history of thyroid pathology were recruited. Biochemical markers, insulin, 25-OH vitamin D, thyroid parameters (TSH, FT3, FT4, TPO antibodies, TG antibodies) and VFT were measured. Serum MCP-1 evaluated the inflammation. A HOMA-IR cut-off value of 2.5 defined IR. Most patients had severe (70.3%) or moderate (25.3%) vitamin D deficiency. Vitamin D level was negatively associated with BMI (p?=?.043) and during the cold season with VFT (p?=?.009). Vitamin D deficiency correlated with Hashimoto’s thyroiditis prevalence during the warm season (p?=?.047) and was a risk factor for its occurrence (p?=?.021). At 15?ng/mL cut-off value, vitamin D was negatively correlated with MCP-1 (p?=?.0006). Also, MCP-1 was positive correlated with HOMA- IR (p?=?.042), TPO-Ab levels (p?=?.011) and with Hashimoto’s thyroiditis (p?=?.027). MCP-1 was a risk factor for vitamin D deficiency (p?相似文献   

Is insulin sensitivity a causal intermediate in the relationship between alcohol consumption and carotid atherosclerosis?: the insulin resistance and atherosclerosis study

OBJECTIVE: A J-shaped association has been demonstrated between alcohol consumption and atherosclerosis. Insulin resistance, also a risk factor for atherosclerosis, has been shown to have a similar J-shaped association with alcohol intake. This raises the question of whether insulin sensitivity (S(I)) is a causal intermediate in the alcohol-atherosclerosis relationship. RESEARCH DESIGN AND METHODS: The Insulin Resistance Atherosclerosis Study was a multicenter cohort study designed to investigate relationships among S(I), risk factors for cardiovascular disease, and carotid artery atherosclerosis. Using regression analysis, we tested whether adjustment for S(I) attenuated the alcohol-atherosclerosis relationship observed at baseline. RESULTS: A J-shaped association was observed between alcohol consumption and common carotid artery intimal medial thickness. The protective aspect of the alcohol-atherosclerosis relationship was attenuated by 25% after the adjustment for S(I). However, an interaction was observed between alcohol consumption and glucose tolerance (GT) status. In comparison with never drinkers, all levels of alcohol consumption were associated with less atherosclerosis in participants with normal GT status. Participants with impaired GT status (but not diabetes) demonstrated a J-shaped alcohol-atherosclerosis association. All levels of alcohol consumption were associated with more atherosclerosis in participants with diabetes. CONCLUSIONS: S(I) may be a causal intermediate at protective levels of alcohol intake, but an alcohol-GT interaction precluded a definitive conclusion. Moderate alcohol consumption may increase the risk of atherosclerosis in people with diabetes. These findings contrast with previous reports and do not support current recommendations regarding moderate alcohol consumption in people with diabetes. More research is needed to clarify this issue.     

Blood coagulation and fibrinolysis in acute ischaemic and haemorrhagic (intracerebral and subarachnoid haemorrhage) stroke: does decreased plasmin inhibitor indicate increased fibrinolysis in subarachnoid haemorrhage compared to other types of stroke?

Ischaemic and haemorrhagic stroke may cause haemostatic abnormalities, apart from concomitant brain damage. In this study, some blood coagulation and fibrinolysis parameters were investigated in 30 patients with ischaemic stroke (atherothrombotic) and 30 with haemorrhagic (20 with intracerebral and 10 with subarachnoid haemorrhage) stroke. The following parameters were determined within the first 24h after stroke: prothrombin time (PT%). activated partial thromboplastin time (aPTT). fibrinogen, activity of FVII, antithrombin. plasmin inhibitor (PI) and fibrin D-dimer. Significant decreases in PT%, FVII activity and antithrombin as well as an increase in fibrinogen and D-dimer were noticed in ischaemic stroke and in both groups of patients with haemorrhagic stroke. PI levels were significantly lower in subarachnoid haemorrhage patients compared with those in controls and those in both the intracerebral haemorrhage and the ischaemic stroke patients. With the exception of this difference, there were no other differences between ischaemic stroke and the two types of haemorrhagic stroke. This could indicate that haemostatic abnormalities are a consequence of brain damage rather than primary haemostatic activation during thrombosis and/or bleeding in the acute phase of stroke. A decrease in the plasmin inhibitor could suggest excessive fibrinolysis in subarachnoid haemorrhage.     

Understanding insulin resistance. What are the clinical implications?

Insulin resistance is an important clinical issue in patients with other prominent components of metabolic syndrome, such as central adiposity and diabetes. However, its presence may be less evident in patients who are neither obese nor diabetic. Is measurement of insulin resistance important in clinical practice? How might its presence change management in individual patients? In this concise review, Dr Sivitz discusses the underlying mechanisms involved in insulin resistance, the issues surrounding assessment, and the implications for management in patients in whom insulin resistance is either detected or suspected.     

Severe sepsis, coagulation, and fibrinolysis: Dead end or one way?

It was suggested more than 30 yrs ago that inhibition of the clotting cascade by natural anticoagulants could decrease the high mortality observed in patients suffering from severe sepsis and septic shock. Unfortunately, this therapeutic "paradigm" has led to a dead end, illustrated by the failure of all randomized trials and the recent withdrawal of recombinant activated protein C. Should we now definitely give up trying to treat septic coagulation disturbances or is there any therapeutic alternative?     

Association between early glycemic control and improvements in markers of coagulation and fibrinolysis in patients with septic shock–induced stress hyperglycemia

Purpose

The purpose of this study is to evaluate the coagulation and inflammatory profiles in septic shock patients with baseline hyperglycemia under glycemic control.

Methods

Prospective, observational study conducted in an intensive care unit of a university hospital, including 41 septic shock nondiabetic patients with hyperglycemia (n = 21) or normoglycemia (n = 20) profiles at baseline. Hyperglycemic patients received a glucose control protocol (target glycemia, < 150 mg/dL). Metabolic, inflammatory, and coagulation markers were measured at baseline and after 24 hours.

Results

Median glycemic values between groups were different at baseline but not after 24 hours. Baseline coagulation profile was similar in both groups with elevated levels of coagulation markers, reduced factor VII, protein C, and antithrombin activities and fibrinolysis impairment. Normoglycemic patients had unchanged coagulation markers after 24 hours. After treatment, previously hyperglycemic patients exhibited increased plasminogen concentrations (P = .03) and reduced levels of plasminogen activator inhibitor 1 (P = .01) and tissue plasminogen activator (P = .03) as compared with baseline. They also had higher factor VII (P = .03), protein C (P = .04), and antithrombin (P = .04) activities than normoglycemic patients. Inflammatory markers were elevated in both groups and improved after 24 hours, independently of the glycemic profile.

Conclusions

Glycemic control during septic shock is associated with improvements in coagulation and fibrinolysis parameters compared with baseline and normoglycemic patients.     

Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents?

OBJECTIVE: Obesity is often associated with insulin resistance and the components of the metabolic syndrome. However, wide variations in insulin sensitivity are noted in obese youth. It is not clear if greater insulin resistance confers a higher risk of cardiovascular comorbidities and risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: We investigated physical and metabolic features of 54 obese adolescents. Subsequently, we pair matched 17 moderately insulin-resistant (MIR group) to 17 severely insulin-resistant (SIR group) youth based on cut points for insulin sensitivity (MIR group insulin sensitivity within 2 SDs and SIR group <2 SDs of normal-weight adolescent values). We evaluated differences in body composition (dual-energy X-ray absorptiometry), abdominal fat (computed tomography scan), cardiorespiratory fitness (CRF) (Vo(2max) on a treadmill), insulin sensitivity and secretion (hyperinsulinemic-euglycemic and hyperglycemic clamps), substrate utilization (indirect calorimetry), and fasting adiponectin and lipid profile. RESULTS: SIR youth had higher visceral adiposity (78.3 +/- 6.9 vs. 60.3 +/- 6.9 cm(2), P = 0.017) and waist-to-hip ratio (0.91 +/- 0.01 vs. 0.86 +/- 0.02, P = 0.026) and lower HDL (1.0 +/- 0.03 vs. 1.16 +/- 0.06 mmol/l, P = 0.015) than pair-matched MIR subjects. There was a tendency for adiponectin (6.1 +/- 0.5 vs. 8.6 +/- 1.1 microg/ml, P = 0.079) and CRF (49.9 +/- 3.2 vs. 55.2 +/- 3.5 ml x min(-1) x kg(-1) fat-free mass, P = 0.09) to be lower in SIR subjects. SIR youth also had an impaired balance between insulin sensitivity and beta-cell compensation with a lower glucose disposition index. CONCLUSIONS: Despite similar BMI, the degree of insulin resistance impacts the risk for obesity-related metabolic comorbidities. The SIR youth are at greater risk for type 2 diabetes and cardiovascular disease.     

Eosinophilic oesophagitis: a common cause of dysphagia in young adults?

Eosinophilic oesophagitis (EO) is an increasingly recognised chronic, relapsing inflammatory condition of the oesophagus. There has been a mini-epidemic of EO in the last decade. The incidence of this condition is higher in children and is commoner in males. There is either a family or personal history of atopic conditions present in a significant number of patients and can also be familial in up to 10%. The classical symptom in an adult is chronic, intermittent solid-food dysphagia and food impaction, often necessitating emergency endoscopic removal. Despite the history of dysphagia for a number of years, patients remain well with no weight loss, which can mislead clinicians to diagnose a functional problem with a resulting delay in the diagnosis. There are various endoscopic features of EO; commonly multiple rings and linear furrows, though these can be subtle and the mucosa may be macroscopically normal. The hallmark of this condition is the histological presence of > or =15 eosinophils/high power field (HPF) in the oesophageal mucosa. Therapeutic options include avoidance of dietary allergens, topical or systemic steroids, Montelukast, Mepolizumab (anti-IL-5 antibody) and endoscopic dilation of strictures unresponsive to medical therapy.     

Effects of metformin and rosiglitazone on peripheral insulin resistance and β-cell function in obesity: a double-blind, randomized, controlled study

Metformin and rosiglitazone combination therapy is known to improve insulin resistance and postpone diabetes mellitus development in subjects with impaired glucose tolerance. This double-blind, randomized, controlled study assessed this combination therapy for preventing type 2 diabetes in obese subjects with hyperinsulinaemia. Subjects received metformin (500 mg three times daily, orally) plus either rosiglitazone (4 mg once daily, orally; n = 94) or placebo (n = 95) and were followed for 6 months. Blood pressure, body fat, body mass index (BMI), lipid and insulin levels were recorded pre- and post-treatment. Metformin plus rosiglitazone significantly decreased blood pressure, lipids, BMI, and fasting and postmeal insulin levels. Metformin plus placebo led to a significant decrease in blood pressure, BMI and lipid levels, but fasting and postmeal insulin levels were unchanged. Adverse events were similar between the two groups. The metformin and rosiglitazone combination increased insulin sensitivity and β-cell function recovered. This approach may represent a therapeutic option for preventing development of type 2 diabetes in obese subjects with hyperinsulinaemia.