Cholecystokinin (CCK) decreases meal size through activation of CCK-A receptors on vagal afferents. We tested the hypothesis that the selective CCK-A agonist GI181771X induces weight loss in obese patients. Patients with body mass index > or = 30 or > or = 27 kg/m2 with concomitant risk factors were randomized to 24-week, double-blind treatment with different GI181771X doses or matching placebo together with a hypocaloric diet. The primary efficacy end point was the absolute change in body weight. To monitor pancreatic and gallbladder effects, patients underwent abdominal ultrasound and magnetic resonance imaging before and after treatment. We randomized 701 patients to double-blind treatment. GI181771X did not reduce body weight and had no effect on waist circumference or other cardiometabolic risk markers. Gastrointestinal side effects were more common with GI181771X than with placebo treatment, whereas hepatobiliary or pancreatic abnormalities did not occur. CCK-A by itself does not have a central role in long-term energy balance.
Consistency in the amount and source of carbohydrate intake from day-to-day is associated with improved blood glucose control in people with type 1 diabetes, a result which supports continued educational efforts to achieve adherence to a diabetes diet plan. This conclusion may not apply to people on intensified insulin therapy who adjust their insulin dose based on their actual carbohydrate intake at each meal.
Type 2 diabetes is caused by progressively increasing insulin resistance coupled with deteriorating beta-cell function, and there is a growing body of evidence to suggest that both of these defects precede hyperglycaemia by many years. Several studies have demonstrated the importance of maintaining beta-cell function in patients with Type 2 diabetes. This review explores parameters used to indicate beta-cell dysfunction, in Type 2 diabetes and in individuals with a predisposition to the disease. A genetic element undoubtedly underlies beta-cell dysfunction; however, a number of modifiable components are also associated with beta-cell deterioration, such as chronic hyperglycaemia and elevated free fatty acids. There is also evidence for a link between pro-inflammatory cytokines and impairment of insulin-signalling pathways in the beta-cell, and the potential role of islet amyloid deposition in beta-cell deterioration continues to be a subject for debate. The thiazolidinediones are a class of agents that have demonstrated clinical improvements in indices of beta-cell dysfunction and have the potential to improve beta-cell function. Data are accumulating to show that this therapeutic group offers a number of advantages over traditionally employed oral agents, and these data demonstrate the growing importance of thiazolidinediones in Type 2 diabetes management.
Because the exact site of thyroid hormone absorption in man is not known, we assessed the absorption of oral [125I]Na-L-T4 in patients with varying lengths of intact bowel and correlated this absorption with bowel length. Two normal subjects and five patients with surgical bowel resections, all of whom were euthyroid, were studied. Each received a tracer dose of [125I]Na-L-T4 orally, and serial samples of serum were assayed for radioactivity both with and without butanol extraction. The peak serum radioactivity in normal subjects occurred 2 h post ingestion and was 15% and 17% of the administered dose per liter serum and 11% and 13%/liter serum in butanol-extracted serum, respectively. In patients with shortened bowel, the peak radioactivity both in serum and butanol extracted serum was decreased, ranging from 2%-7% and 0%-5%/liter, respectively. There was no absorption of labeled T4 in the patient with a duodenum only. No consistent relationship was found between absorption and bowel length distal to the duodenum.
We studied whether the use of 8 mm insulin pen needles, shorter than the standard 12.7 mm needles, affects glucose control in obese and non‐obese people with type 1 or type 2 diabetes. A prospective, open‐label, nine‐week, crossover study involved 106 insulin pen‐using patients. During the initial period, all subjects used B‐D brand standard length needles. In the second period, subjects were randomised to either B‐D or NovoFine brand 8 mm pen needles. In the third period, subjects were crossed over to the alternative brand. Fructosamine levels were measured, leakage of insulin from injection sites was quantified, and pain was assessed. Glucose control was not altered in either obese or nonobese subgroups after switching to either brand of 8 mm needle. However, a few individuals, most of whom were obese, experienced a clinically significant increase in fructosamine levels after switching to an 8 mm needle. B‐D 8 mm needles were significantly less painful than either of the other needles tested. Obese subjects were significantly more likely to experience insulin leakage from their injection sites compared to non‐obese people, but the leakage was not significantly correlated with changes in fructosamine levels. Non‐obese people with type 1 or type 2 diabetes can switch to 8 mm insulin pen needles without compromising their glucose control and with less pain. Some obese patients who switch to 8 mm needles may have a higher risk of poorer glucose control, and should therefore consult with their healthcare professional. All patients should carefully monitor their blood glucose when changing to a shorter needle.
Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of type 2 diabetes mellitus. The GI safety of albiglutide, a once-weekly GLP-1RA, was assessed using data from five phase III studies. In a pooled analysis of four placebo-controlled trials, the most common GI AEs were diarrhoea (albiglutide, 14.5% vs. placebo, 11.5%) and nausea (albiglutide, 11.9% vs. placebo, 10.3%), with most patients experiencing 1-2 events. The majority were mild or moderate in intensity and their median duration was 3-4 days. Vomiting occurred in 4.9% of patients in the albiglutide vs. 2.6% in the placebo group. For both albiglutide and placebo, serious GI AEs (2.0% vs. 1.5%) and withdrawals attributable to GI AEs (1.7% vs. 1.5%) were low. In a 32-week trial of albiglutide 50 mg weekly versus liraglutide 1.8 mg daily, nausea occurred in 9.9% of patients in the albiglutide group vs. 29.2% in the liraglutide group. Vomiting occurred in 5.0% in the albiglutide vs. 9.3% in the liraglutide group. In conclusion, albiglutide has an acceptable GI tolerability profile, with nausea and vomiting rates slightly higher than those for placebo but lower than those for liraglutide.
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