The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study

OBJECTIVERoux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.RESEARCH DESIGN AND METHODSA total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.RESULTSBoth groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.CONCLUSIONSThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.     

Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells.

Abnormal regional increases in DNA methylation, which have potential for causing gene inactivation and chromosomal instability, are consistently found in immortalized and tumorigenic cells. Increased DNA methyltransferase activity, which is also a characteristic of such cells, is a candidate to mediate these abnormal DNA methylation patterns. We now show that, in NIH 3T3 mouse fibroblasts, constitutive overexpression of an exogenous mouse DNA methyltransferase gene results in a marked increase in overall DNA methylation which is accompanied by tumorigenic transformation. These transformation changes can also be elicited by dexamethasone-inducible expression of an exogenous DNA methyltransferase gene. Our findings provide strong evidence that the increase in DNA methyltransferase activity associated with tumor progression could be a key step in carcinogenesis and provide a model system that can be used to further study this possibility.     

Early insulin release following suckling in neonatal lambs and rabbits

Summary Developmental changes in the plasma insulin response to milk ingestion have been determined in neonatal lambs fed by bottle and in naturally suckled infant rabbits. In lambs at 4 days of age and older plasma insulin increased within 5 min of suckling and declined again before increasing to a second peak 60 to 120 min after the feed. The early insulin peak was not associated with any change in plasma glucose and was absent in lambs at 1 day of age. When the early insulin peak was absent the increase in plasma glucose following the meal was greater. The early, apparently reflex, release of insulin also occurred in some sham-fed lambs. Atropine administration before feeding abolished the early peak in insulin. A marked early peak of insulin release, not accompanied by any consistent change in plasma glucose, was also observed in naturally-suckled infant rabbits at 1, 5, 10 and 15 days after birth.     

Task shifting for cataract surgery in eastern Africa: productivity and attrition of non-physician cataract surgeons in Kenya,Malawi and Tanzania

Background

This project examined the surgical productivity and attrition of non-physician cataract surgeons (NPCSs) in Tanzania, Malawi, and Kenya.

Methods

Baseline (2008-9) data on training, support, and productivity (annual cataract surgery rate) were collected from officially trained NPCSs using mailed questionnaires followed by telephone interviews. Telephone interviews were used to collect follow-up data annually on productivity and semi-annually on attrition. A detailed telephone interview was conducted if a surgeon left his/her post. Data were entered into and analysed using STATA.

Results

Among the 135 NPCSs, 129 were enrolled in the study (Kenya 88, Tanzania 38, and Malawi 3) mean age 42 years; average time since completing training 6.6 years. Employment was in District 44%, Regional 24% or mission/ private 32% hospitals. Small incision cataract surgery was practiced by 38% of the NPCSs. The mean cataract surgery rate was 188/year, median 76 (range 0-1700). For 39 (31%) NPCSs their surgical rate was more than 200/year. Approximately 22% in Kenya and 25% in Tanzania had years where the cataract surgical rate was zero. About 11% of the surgeons had no support staff.Factors significantly associated with increased productivity were: 1) located at a regional or private/mission hospital compared to a district hospital (OR = 8.26; 95 % CI 2.89 – 23.81); 2) 3 or more nurses in the eye unit (OR = 8.69; 95% CI 3.27-23.15); 3) 3 or more cataract surgical sets (OR = 3.26; 95% CI 1.48-7.16); 4) a separate eye theatre (OR = 5.41; 95% CI 2.15-13.65); 5) a surgical outreach program (OR = 4.44; 95% CI 1.88-10.52); and 6) providing transport for patients to hospital (OR = 6.39; 95% CI 2.62-15.59). The associations were similar for baseline and follow-up assessments. Attrition during the 3 years occurred in 13 surgeons (10.3%) and was due to retirement or promotion to administration.

Conclusions

High quality training is necessary but not sufficient to result in cataract surgical activity that meets population needs and maintains surgical skill. Needed are supporting institutions and staff, functioning equipment and programs to recruit and transport patients.

     

Neurobehavioral profiles of children with neurofibromatosis 1 referred for learning disabilities are sex-specific

We compared neurobehavioral profiles of 10 children with neurofibromatosis 1 (NF-1) referred for evaluation of learning disabilities (NF/LD) to those of learning disabled children without known genetic disease (LD), matched for age, sex, and estimated IQ. It was hypothesized that the NF/LD children would exhibit a neurobehavioral profile diagnostic of compromise of frontal/subcortical brain systems while those of the case controls would be heterogeneous. Records from a clinic data base were reviewed retrospectively for the neurological and neuropsychological components of an interdisciplinary learning disabilities evaluation. Neurological abnormalities were more frequent in the NF/LD group, involving gross and fine motor coordination, praxis, and megencephaly. As predicted, clinical neuropsychological diagnostic ratings and composite neurobehavioral observation scores were consistent with compromise of frontal systems in the NF/LD group. An unanticipated finding was that outcomes in the NF/LD group were sex dependent: Megencephaly was observed in females only; and the frontal/subcortical neurobehavioral profile was more consistently observed in females. Females with NF-1 with megencephaly may be at increased risk for a neurobehavioral syndrome contributing to LD that is consistent with compromise of frontal/subcortical brain systems. © 1996 Wiley-Liss, Inc.