Martin A. Crook

The importance of the refeeding syndrome.

In this review we discuss the refeeding syndrome. This potentially lethal condition can be defined as severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished patients undergoing refeeding, whether orally, enterally, or parenterally. It can be associated with significant morbidity and mortality. Clinical features are fluid-balance abnormalities, abnormal glucose metabolism, hypophosphatemia, hypomagnesemia, and hypokalemia. In addition, thiamine deficiency can occur. We describe which patient groups are more at risk for this syndrome and the clinical management of the condition.

A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism

PURPOSE The role of thyroxine replacement in subclinical hypothyroidism remains unclear. We performed a 6-month randomized, double-blind, placebo-controlled trial to evaluate the effects of thyroxine treatment for mild subclinical hypothyroidism, defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level (0.8-16 ng/dL). SUBJECTS AND METHODS We randomly assigned 40 women with mild subclinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment (n = 23; 50 to 100 microg daily) or placebo (n = 17). Health-related quality of life (Hospital Anxiety and Depression scale, 30-item General Health Questionnaire), fasting lipid profiles, body weight, and resting energy expenditure were measured at baseline and 6 months. RESULTS The most common presenting symptoms were fatigue (n = 33 [83%]) and weight gain (n = 32 [80%]). At presentation, 20 women (50%) had elevated anxiety scores and 22 (56%) had elevated scores on the General Health Questionnaire. Thirty-five women completed the study. There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic, lipid, or anthropometric variables measured, expressed as the mean change in the thyroxine group minus the mean change in the placebo group: body mass index, -0.3 kg/m(2) (95% confidence interval [CI]: -0.9 to 0.4 kg/m(2)); resting energy expenditure, -0.2 kcal/kg/24 h (95% CI: -1.3 to 1.0 kcal/kg/24 h); and low-density lipoprotein cholesterol, -4 mg/dL (95% CI: -23 to 15 mg/dL). There was a significant worsening in anxiety scores in the thyroxine group (scores increased in 8 of 20 women and were unchanged in 2 of 20) compared with the placebo group (scores increased in 1 of 14 women and were unchanged in 6 of 14; P = 0.03). CONCLUSIONS; We observed no clinically relevant benefits from 6 months of thyroxine treatment in women with mild subclinical hypothyroidism.

Elevated Serum Sialic Acid Concentration in NIDDM and Its Relationship to Blood Pressure and Retinopathy

Objective— In view of the possible link between serum sialic acid and cardiovascular disease in the general population, we investigated whether serum total and lipid-associated sialic concentrations are elevated in NIDDM patients compared with normal subjects. We also investigated how sialic acid levels relate to glycemic control, blood pressure, microalbuminuria, retinopathy, and serum lipid levels. Research Design and Methods— We selected 20 NIDDM patients at random and matched them for age and sex with 20 normal subjects. The patients also had a similar BMI as the control subjects. A first morning blood sample was taken for sialic acid, glucose, fructosamine, and lipid analysis, as was a first morning urine sample for assessment of microalbuminuria. Retinopathy was assessed by fundoscopy. Results— Both total and lipid-associated sialic acid levels were elevated in the NIDDM patients compared with control subjects (mean ± SD, total: 0.74 ± 0.11 vs. 0.60 ± 0.22 g/L, P < 0.02; lipid-associated: 0.18 ± 0.04 vs 0.12 ± 0.04 g/L, P < 0.001). Total serum sialic acid was correlated with systolic blood pressure (r = 0.58, P < 0.01) and diastolic blood pressure (r = 0.58, P < 0.02). There was no significant relationship of total sialic acid with age, duration of diabetes, BMI, microalbuminuria, serum triglyceride, blood glucose, or serum fructosamine. A relationship of lipid-associated sialic acid levels and systolic blood pressure did not reach significance (P = 0.09). In 9 patients with background retinopathy with or without maculopathy, the total serum sialic acid concentration was higher than in those without retinopathy (0.81 ± 0.09 vs. 0.69 ± 0.10 g/L, P < 0.008). Lipid-associated sialic acid levels were similar in those with and without retinopathy. (The conversion factor for standard units to SI units is 1 gL = 3.2 mM.) Conclusions— Total serum sialic acid levels were significantly elevated in a relatively small group of NIDDM patients and were correlated with hypertension and retinopathy. A larger study of circulating sialic acid concentrations as a risk factor for the development or marker of diabetic angiopathy is therefore justified.

Serum Sialic Acid, a Risk Factor for Cardiovascular Disease, Is Increased in IDDM Patients With Microalbuminuria and Clinical Proteinuria

OBJECTIVE An elevated serum sialic acid concentration has recently beenshown to be a potent cardiovascular risk factor in the general population. Because clinical proteinuria is associated with a high frequency of cardiovascular disease, and because microalbuminuria predicts the development of renal and cardiovascular disease in diabetes, we investigated whether serum sialic acid levels are increased in insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria or clinical proteinuria. RESEARCH DESIGN AND METHODS We studied 23 patients with IDDM who had a normal urinary albumin excretion rate, 23 patients who had microalbuminuria, and 23 patients with clinical proteinuria. The patients were matched for age, sex, duration of diabetes, GHb levels, and body mass index (BMI). Fasting blood samples were taken for measurement of sialic acid, cholesterol, triglyceride, creatinine, and GHb. RESULTS Serum sialic acid was significantly higher in the microalbuminuric patients compared with the normoalbuminuric group (mean ± SD: 1.93 ± 0.26 vs. 1.76 ± 0.27 mM, P < 0.01). Moreover, serum sialic acid was also significantly higher in the group with clinical proteinuria compared with the microalbuminuric patients (2.34 ± 0.24 vs. 1.93 ± 0.26 mM, P < 0.001). Serum sialic acid was not related independently to age, BMI, diabetes duration, GHb, blood pressure, serum cholesterol, triglyceride, or creatinine concentration in any of the diabetic groups. CONCLUSIONS These observations suggest that the serum sialic acid concentration is raised in IDDM patients with both microalbuminuria and clinicalproteinuria and may play a role as a cardiovascular risk factor or disease marker in these conditions.

Apolipoprotein E gene polymorphisms are associated with psoriasis but do not determine disease response to acitretin

Background  Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define the three common ApoE alleles e2, e3 and e4.

Waist-hip ratio and low HDL predict the risk of coronary artery disease in Pakistanis

SUMMARY Objective: To establish risk factor causal associations for coronary artery disease (CAD) in the native Pakistani population. Methods: We conducted a hospital-based, case-control study of 200 cases with angiographically documented CAD and 200 age-and sex-matched controls without angiographic evidence of CAD. Patients on lipid lowering therapy were excluded. Lifestyle, anthropometric and biochemical risk factors were assessed in both groups. Results: The presence of CAD was associated with current, past or passive smoking, a history of diabetes and high blood pressure, a positive family history of CAD, body fat percentage, waist-hip ratio (WHR), low apolipoprotein A1 or low HDL, lipoprotein (a), glucose, insulin, insulin resistance, C-reactive protein (CRP), total cholesterol to HDL ratio (TC/HDL) and creatinine on univariate conditional logistic regression analysis. In multiple regression analysis, significant independent associations were found with low HDL (OR 0.11; 95% CI 0.04–0.34; p < 0.001) positive family history (OR 1.79; 95% CI 1.09-2.93; p = 0.02), CRP (OR 1.45; 95% CI 1.19–1.75; p < 0.001) and WHR (OR 1.04; 95% CI 1.01-1.08; p = 0.01). Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. Quantitative angiographic data showed associations with age (p = 0.01), the duration of diabetes (p = 0.04), WHR (p = 0.06), low HDL (p < 0.001), lipoprotein (a) (p = 0.001), creatinine (p < 0.001) and CRP (p = 0.007). Results indicate that total and LDL cholesterol were not significant risk factors in this study; levels were below currently accepted thresholds for treatment. Conclusions: The cardiovascular risk profile in this population is consistent with metabolic syndrome where low HDL and WHR can be used to predict the risk of CAD. Results suggest the need to redefine the currently practised approach to CAD management in this population to fit local needs.

Efficacy of ezetimibe in patients with statin-resistant and statin-intolerant familial hyperlipidaemias

ABSTRACT Objective : To investigate the efficacy of the cholesterol absorption inhibitor ezetimibe in patients with refractory familial hyperlipidaemia or intolerant to statin therapy. Methods : This prospective study assessed the safety and efficacy of ezetimibe in 200 patients with refractory familial hyperlipidaemias not achieving a low-density-lipoprotein (LDL) cholesterol < 3 mmol/L (116 mg/dL) including 22% intolerant to all statin therapy, many consuming sterol-containing products. Results : Ezetimibe monotherapy resulted in 7% and 11% reductions in LDL-cholesterol and apolipoprotein B respectively. Ezetimibe-statin combination therapy reduced LDL-cholesterol by an additional 11 ± 27% and apolipoprotein B by 11 (+79 to –18)%. There was a similar response between various sub-groups but a wide variation within groups with the greatest effect seen in patients under-responding to statins. The number of patients achieving the LDL‐C target of 3 mmol/L rose from 5.5% to 18%. Non-significant effects included a 5 (+78 to –470)% reduction in triglycerides, 8 ± 36% increment in HDL‐cholesterol, 21 (+35 to –82)% reduction in C-reactive protein and a 1 (+20 to –50)% increase in alanine transaminase. No effects were seen on creatinine, creatine kinase, or insulin resistance. Fourteen patients (7%) discontinued ezetimibe: seven due to gastrointestinal side-effects, one patient developed an ezetimibe-induced hypercholesterolaemia (× 1.5), one developed ezetimibe-induced hypertriglyceridaemia (× 7) and five discontinued for other reasons. Conclusion : Ezetimibe is a useful addition to statins in patients with familial hyperlipidaemias but shows a highly variable response profile.

A prospective case-controlled cohort study of endothelial function in patients with moderate to severe psoriasis

Background  There is well‐documented evidence that patients with moderate and severe psoriasis have a significantly increased risk of cardiovascular disease (CVD). While this risk can, at least in part, be attributed to the high prevalence of traditional risk factors in the population with psoriasis, some epidemiological evidence suggests it may be independent of these.

Lipid Clearance and Total Parenteral Nutrition: The Importance of Monitoring Plasma Lipids

Lipid provides two major advantages for total parenteral nutrition (TPN). First, it provides essential fatty acids, thus avoiding essential fatty acid deficiency, and secondly, it is a useful energy source, providing 9 kcal/g. However, we describe a patient who had TPN containing Intralipid, where problems of lipid clearance developed. We also review the literature of lipid clearance problems in TPN patients and suggest ways by which such problems can be managed. We suggest that patients taking TPN should have their plasma lipids (triacylglycerols) measured before and during TPN initiation. This is particularly important in patients who are at high risk of impaired fat clearance, such as those who are hyperlipidemic, diabetic, septic, or with impaired renal or hepatic function, or those who are critically ill.

Metabolic syndrome and risk of coronary heart disease in a Pakistani cohort

Objective: To assess the relation of the metabolic insulin resistance syndrome (M-IRS) with coronary heart disease (CHD) in Pakistani patients. Subjects: 200 patients with angiographic disease (CHD(+)) matched with 200 patients with chest pain without occlusive disease (CHD(−)). Design: Prospective case–control study. Setting: Tertiary referral cardiology unit in Pakistan. Results: M-IRS was present in 37% of CHD(+) versus 27% of CHD(−) patients by criteria for white patients or 47% versus 42%, respectively, by Asian criteria (p < 0.001). After adjustment for other risk factors, M-IRS was not a significant predictor for CHD or angiographic disease. Age (p  =  0.03), smoking (p < 0.001), diabetes-years (p = 0.003), sialic acid (p  =  0.01), and creatinine (p  =  0.008) accounted for the excess risk of CHD. Similarly, age (p  =  0.005), creatinine (p < 0.001), cigarette pack-years (p  =  0.02), diabetes-years (p  =  0.003), and sialic acid (p  =  0.08) were predictors of greater angiographic disease. M-IRS differed between Pakistani and white patients, as waist circumference correlated weakly (r  =  −0.03–0.08, p  =  0.45–0.52) with triglycerides, high density lipoprotein cholesterol, systolic blood pressure, or glucose. Sialic acid was the only inflammatory marker associated with M-IRS. Conclusions: Despite strong associations between individual risk factors associated with M-IRS and a univariate association between M-IRS and CHD in native Pakistanis, the principal discriminant risk factors in this group are age, smoking, inflammation, diabetes-years, and impaired renal function. The poor sensitivity of M-IRS for CHD reflects the high underlying prevalence of M-IRS, thus reducing sensitivity, confounding by other urban lifestyle traits, or a lack of association of waist circumference with M-IRS risk factors. The definition of M-IRS may have to be revised to increase its power as a discriminant risk factor for CHD in Pakistani populations.