Edited by Helaine E. Resnick, PhD, MPH
“Obese” and “Lean” Bacteria: Growing Interest in the Gut Microbiome
A review in this issue of Diabetes Care (p. 159) summarizes an increasing body of evidence linking features of the gut microbiome to a number of obesity-related conditions, including abnormalities of glucose metabolism. Under normal conditions, there is a symbiotic relationship between bacteria that inhabit the gut and the humans who host them. However, studies in both rodents and humans have shown that the composition of gut microbiota differs between lean and obese subjects—a persistent observation suggesting that the gut microbiome may play a meaningful role in energy balance. It has been postulated that an “obese microbiome” may be particularly efficient at deriving energy from the diet, and this efficiency may ultimately lead to obesity and obesity-related conditions such as diabetes. Fecal microbiota transplantation (FMT) has been used in both rodents and humans to begin to understand how lean and obese microbiota may influence various physiological characteristics. Recent FMT studies in insulin-resistant humans have shown that FMT from lean donors resulted in improvements in peripheral insulin sensitivity and increases in the diversity of subjects’ intestinal microbiota. A potentially important aspect of this observation was that the increased diversity of the gut microbiome included an increase in butyrate-producing bacteria. This is significant because butyrate and acetate and propionate are short-chain fatty acids (SCFAs) that are known to be important in energy metabolism. Studies in mice have shown that oral butyrate increases insulin sensitivity and energy expenditure by increasing mitochondrial function. Although these observations may offer a potential connection between specific features of the gut microbiome and mechanisms that underpin human obesity, a causal link between specific intestinal bacteria, SCFA, and metabolic function has not been established. Moving this line of investigation forward will require innovative studies that focus on SCFA supplementation or FMT from various donors to understand how manipulation of the gut microbiome may be harnessed to address the stubborn problems of obesity and diabetes. — Helaine E. Resnick, PhD, MPH
Extensive Geographic Variation in Diabetes Ascertainment in China
Data from more than 98,000 Chinese adults living in 162 areas across China provide new detail on the landscape of diabetes prevalence and ascertainment in this large and diverse country. The new report (p. 72) relied on data from China’s National Disease Surveillance Point (DSP) System, a nationally representative health survey that covers 7% of China’s population. This survey contains information for physician-diagnosed diabetes as well as blood specimens that were used to determine respondents with undiagnosed diabetes. An important aspect of the new research is that it combines person-level data with geographic information, thereby providing a nuanced perspective on the determinants of diabetes across China. Data on diabetes prevalence (diagnosed plus undiagnosed) showed that urban areas tended to have more diabetes than rural ones. In Beijing, prevalence ranged from 15.4 to 22.1%, whereas in Tibet, prevalence was 5.4–9.2%. These findings support the idea that in China, diabetes is more common in areas that are characterized by greater economic advantage or affluence. Although person-level factors such as health literacy attenuated the association between geographic location and diabetes prevalence, there was still meaningful variation at the provincial, town, and village levels. A different picture emerged for diabetes ascertainment—the proportion of people with diabetes whose condition was diagnosed. There were considerable disparities between the rural and urban areas, with people in rural areas being considerably less likely to be diagnosed than their urban counterparts. Adjustment for person-level factors had only a minor influence on these findings, an observation suggesting that one objective of resource allocation for diabetes diagnosis and treatment in China should focus on reducing the gap of diabetes ascertainment in rural areas. — Helaine E. Resnick, PhD, MPH
ORIGIN Results Provide Insight for Hypoglycemia Risk Reduction
Findings from the ORIGIN trial (p. 22) show a distinction between risk factors for severe and nonsevere hypoglycemia. The ORIGIN trial randomized more than 12,000 participants with glucose abnormalities to receive either insulin glargine (in addition to current treatment) or to a standard care arm that began with oral therapy. Although the main outcome in this trial was a composite of nonfatal MI, stroke, or CV death, the detailed information that was collected on hypoglycemic events provided a unique opportunity to examine the distinction between severe and nonsevere hypoglycemia in relation to the intervention arm to which participants were randomized, as well as other clinical characteristics. Nonsevere hypoglycemia was defined as a symptomatic event with a concurrent glucose measurement of ≤3.0 mmol/L that did not require the assistance of another person. A severe event was defined as plasma glucose ≤2.0 mmol/L or an event that required assistance with prompt recovery with oral administration of carbohydrate, intravenous glucose, or glucagon. Overall, 41% of the cohort experienced at least one hypoglycemic event, but larger proportions of participants in the insulin glargine arm experienced both severe and nonsevere events compared with standard care. Although multivariate analyses showed that patients who were allocated to the insulin glargine arm and those who were taking sulfonylureas were more likely to have both severe and nonsevere events, these analyses also highlighted divergent relationships between other patient characteristics and the severity of these events. Younger patients were more likely to have nonsevere events, while older patients, those with lower educational attainment, and those with higher cognitive impairment were more likely to experience severe events. These intriguing results support the idea that below-normal glucose levels that do or do not require assistance happen among different patients. These distinctions have implications for clinical management, and they may help tailor therapy and education in ways that minimize risk. — Helaine E. Resnick, PhD, MPH
Promising Results for Internet-Based Weight-Loss Program
Results from a randomized trial that compared weight loss between people who received an Internet-based, behavior-focused weight-loss program and those who simply accessed weight loss–related educational material online showed that at 3 and 6 months, those in the behavior-focused program had higher mean weight loss and were more likely to have lost 5% of their body weight. The new report (p. 9) is based on data from 154 patients aged 18–70 years with BMI between 25 and 45 kg/m2 at baseline. Participants were referred from their physicians and then randomized to one of the two online programs. The first was a behavior-focused program that involved submission of self-monitoring data and receipt of weekly behavioral information, coaching, and feedback. The control program featured access to a website that contained educational material on weight loss, but no interactive features. The trial’s primary outcome was weight loss at 3 months, and secondary outcomes focused on maintenance of weight loss at 6 months and changes in weight loss–related behaviors. Participants in the behavior-focused intervention had greater weight loss at both 3 (5.5 vs. 1.3 kg) and 6 (5.4 vs. 1.3 kg) months. In addition, 53% of those in the behavior-focused intervention lost 5% of their body weight at 3 months, and the proportion remained high at 48% at 6 months. Notably, 21% of people in the behavior-focused intervention lost 10% or more of their body weight at the two time points. Although weight-loss behaviors increased in both intervention groups during the study, these favorable behaviors improved more frequently in the behavior-focused Internet intervention group. Some behaviors, such as reducing caloric and fat intake, persisted to a greater extent at 6 months. Results from this new trial demonstrate that when referred by a physician, overweight and obese adults accessed an online, behavior-focused weight-loss intervention with great frequency, and use of this resource resulted in clinically meaningful weight loss. Given the extent of the obesity problem in the U.S. and elsewhere, these data suggest that technological supports to promote weight loss may be an effective strategy that can be added to providers’ toolboxes. — Helaine E. Resnick, PhD, MPH
