Hypoglycemia in Insulin-Treated Adults on Established Nasogastric Feeding in the General Ward: A Systematic Review.

PURPOSE: This study aimed to address 2 questions: First, what are the existing summary statistics of frequency of hypoglycemia in insulin-treated adults on established nasogastric feeding in the general ward? Second, to what extent does lack of homogeneity in defining, identifying, and reporting hypoglycemia affect these statistics? METHODS: A systematic review of the literature documenting hypoglycemia in insulin-treated adults on nasogastric feeding for ≥ 3 days in the general ward was carried out. Data sources were PubMed, Embase, ProQuest, Cochrane, Directory of Open Access Journals, and PLoS. Search period was 1999 onward, postdating introduction of analog insulin. RESULTS: Initially, 231 studies were identified, with 9 judged suitable for inclusion, according to inclusion/exclusion criteria. All included studies had as their primary objective the assessment of efficacy of insulin/feed regimens in the target population. Studies exhibited major heterogeneity. Definitions of hypoglycemia varied from < 60 mg/dL (3.3 mmol/L) to < 80 mg/dL (4.4 mmol/L), and 5 methods of reporting frequency of hypoglycemia were utilized, precluding pooled analysis. A descriptive synthesis of results was generated with some comparable results presented on a modified forest plot, showing 2.1% to 10.2% of patients with a hypoglycemic event and 1.1% to 5.4% blood glucose level < 70 mg/dL (3.9 mmol/L). CONCLUSIONS: Hypoglycemia is not uncommon in this population, but further research is needed for quantification. Standardized documentation and reporting methods incorporating sample size and study duration, such as hypoglycemic events per patient-days, would facilitate interstudy comparisons, as would documentation of hypoglycemia at the 2 most commonly defined levels: < 63 mg/dL (3.5 mmol/L) and < 70 mg/dL (3.9 mmol/L).

Omitting Follow-up Food After Initial Hypoglycaemic Treatment Does not Increase the Likelihood of Repeat Hypoglycaemia.

INTRODUCTION: Guidelines for self-treatment of hypoglycaemia specify initial treatment with quick-acting carbohydrate until blood glucose levels normalize and then follow-up with longer-acting carbohydrate. The few studies investigating follow-up show 29-57% omission or undertreatment with follow-up carbohydrate but do not investigate the association of this with repeat hypoglycaemia. This study aimed to develop, validate and administer a questionnaire to delineate this association. The timeframe targeted was 2 h post primary hypoglycaemic event (PPHE), the time influenced by long-acting carbohydrate. METHODS: A questionnaire was generated, test-retest reliability assessed, and it was piloted on convenience samples from the target population. The final version was administered to all insulin-treated individuals attending an outpatient diabetes clinic over 4 weeks (169). RESULTS: Questionnaire development: readability (69.6-standard/easy), test-retest reliability (Cohen's kappa 0.57-0.91) and return rate (72.2%) were all acceptable. Questionnaire data: questionnaires were returned by 122 participants (63 males/59 females). Method of insulin administration was subcutaneous insulin injections (91%) and continuous subcutaneous insulin infusion (CSII) (9%). Repeat hypoglycaemia within 2 h PPHE was reported by 8.2% of respondents. There was no significant difference for age, gender and diabetes duration between those reporting repeat hypoglycaemia and those without. Consumption of follow-up longer-acting carbohydrate was reported by 58.2% of responders with 48% of these using long-acting and 52% medium-acting carbohydrate foods. Method of insulin administration and consumption of follow-up food were significantly associated with repeat hypoglycaemia (P = 0.015, 0.039) but presence or absence of symptoms and duration of action of carbohydrate were not significantly associated (P = 0.103, 0.629). Hierarchical logistic regression analysis showed omission of follow-up food PPHE was not a significant predictor of increased likelihood of repeat hypoglycaemia within 2 h PPHE, irrespective of method of insulin administration (P = 0.085). CONCLUSION: This study supports guidelines that recommend judicious, rather than routine use of follow-up longer-acting carbohydrate PPHE.

Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study.

OBJECTIVE: Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2)) are at particular cardiovascular risk. Fenofibrate's safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate's effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (aged 50-75 years) with eGFR ≥30 mL/min/1.73 m(2) were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30-59, 60-89, and ≥90 mL/min/1.73 m(2)). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 µmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS: Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80-0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30-59 mL/min/1.73 m(2): 0.68 [0.47-0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m(2): 0.85 [0.70-1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS: Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.

Effect of lowering tumour necrosis factor-alpha on vascular endothelial function in Type II diabetes.

Tumour necrosis factor-alpha (TNF alpha) is a mediator of reactive oxygen species, which are implicated in endothelial dysfunction and atherosclerosis. Type II diabetes is associated with endothelial dysfunction and elevated circulating TNF alpha. We hypothesized that reducing serum levels of TNFalpha, using pentoxifylline, would improve endothelial function. Thirteen subjects [age 58+/-2 (S.E.M.) years] with Type II diabetes (disease duration 74+/-13 months) undertook a randomized, crossover study of 8 weeks pentoxifylline and 8 weeks placebo. Endothelium-dependent and-independent vasodilation in resistance arteries was assessed via bilateral forearm venous occlusion plethysmography during intra-brachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA). High-resolution ultrasound of the brachial artery in response to ischaemia was used to determine endothelium-dependent conduit vessel flow-mediated dilation (FMD), and endothelium-independent conduit function was assessed by sublingual administration of glyceryl trinitrate (GTN). Serum concentrations of TNF alpha were also determined. Pentoxifylline lowered serum TNF alpha from 4.1+/-0.7 to 2.9+/-0.6 pg x ml(-1) (P=0.001). Forearm blood flow (FBF) responses at each dose of ACh did not differ with treatment (P=0.4). Similarly, FBF responses to SNP (P=0.8) and L-NMMA (P=0.2) did not differ. There was also no significant difference in brachial artery diameter during FMD (P=0.2) or GTN administration (P=0.06). Despite lowering serum TNF alpha concentration, pentoxifylline at a dose of 400 mg three times a day for 8 weeks did not improve vascular function in either conduit or resistance vessels in this group of Type II diabetic subjects.

Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular morbidity in diabetic subjects.

In the present study, the determinants of fasting plasma homocysteine in diabetic subjects were examined; whether plasma homocysteine and vascular disease are related and the influence of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate, plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I, n=354; Type II, n=392) were recalled for a cross-sectional survey. Standard methods were used to measure biochemical variables and to characterize vascular disease and MTHFR genotype. Plasma homocysteine was significantly and directly related to age, male sex and serum urea, and inversely related to serum folate and vitamin B12, independently in stepwise regression. When corrected for age and sex, homocysteine was significantly related to hard end points of coronary artery disease and stroke (each P<0.01), remaining significant when additionally adjusted for serum folate (P=0.043 and P=0.019 respectively). Serum folate was not clearly related to these events, although there was a trend to associate with the lower quintile of serum folate. The MTHFR genotype was not a determinant of plasma homocysteine, even in those in the lowest quintile of serum folate, nor of vascular disease. TT homozygosity at residue 677 was associated with elevation of total erythrocyte folate compared with both other genotypes (P<0.0001), almost certainly due to the diversion of 5,10-methylenetetrahydrofolate into derivates subsequent to the partial metabolic block that results from the MTHFR enzyme defect. In conclusion, in this clinic cohort of people with diabetes, vascular disease is related to plasma homocysteine, which is correlated with serum folate. The MTHFR genotype does not significantly influence either plasma homocysteine or vascular disease, despite it being a determinant of erythrocyte folate, which reflects its effect on folate metabolism.