DR. DOMINIC NICHOLAS REEDS, MD

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This randomized trial tested whether six months of cardio and resistance exercise improved brain health and gut bacteria diversity in older adults living with HIV. Both the exercise group and a stretching control group showed modest improvements in thinking speed, body weight, physical fitness, and gut microbiome diversity, suggesting that even light activity may benefit HIV-positive people who were previously sedentary. Brain blood flow did not change in either group, and longer studies with more participants are needed.

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Researchers compared muscle and bone health in people with overweight or obesity who had prediabetes versus those with normal blood sugar but the same body weight. Those with prediabetes had smaller muscle fibers, less bone density, more fat stored inside muscle cells, and faster muscle fatigue — even though their body weight was identical. This shows that early metabolic dysfunction damages muscles and bones beyond what excess weight alone causes.

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This study examined whether heart transplantation fixes the whole-body metabolic problems seen in Barth syndrome, a rare genetic disorder causing heart and muscle disease. Despite improved heart function after transplant, patients who had received a new heart still had the same poor exercise capacity, low muscle mass, abnormal energy production in muscles, and elevated blood lactate as those who had not been transplanted. The findings show that the metabolic defects in Barth syndrome are not caused by heart failure alone and persist even after successful cardiac transplantation.

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This study compared several widely used formulas for assessing how well the pancreas secretes insulin (beta-cell function) across groups ranging from lean and healthy to obese with type 2 diabetes. Different formulas produced contradictory rankings of beta-cell function among the same groups, and none accurately reflected the actual measured relationship between insulin secretion and blood glucose. Standard beta-cell function indices can be misleading and should be interpreted with caution.

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Certain groups — including older adults, racial and ethnic minorities, people with lower incomes, and those in rural areas — are consistently underrepresented in biomedical research, and the COVID-19 pandemic made this problem worse and more consequential. This paper reviews the structural and social barriers that keep these populations out of research studies and proposes a framework called structural competency to help researchers understand and address those barriers. Improving inclusion in research is essential to reducing health inequities.

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HIV-positive people on effective antiretroviral therapy still face higher rates of cognitive decline and reduced brain integrity as they age, and this paper describes the protocol for a clinical trial testing whether six months of aerobic and resistance exercise can improve brain structure, blood flow, and thinking ability in this population. The trial enrolled 150 sedentary adults aged 40 and older with well-controlled HIV and randomized them to exercise training or a stretching control group, measuring fitness, cognition, and brain MRI scans at baseline and follow-up. Results from this trial will inform whether structured exercise programs should be recommended as part of HIV care for older adults.

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This review traces how scientists' understanding of high blood sugar has evolved over the past century, from simple measurements to mechanistic insight into how glucose enters and leaves the bloodstream. It explains how different forms of prediabetes and diabetes arise from distinct disruptions in glucose production, clearance, and tissue uptake. The historical perspective shows how physiological research has shaped current definitions and treatment targets for hyperglycemia.

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People with well-controlled HIV still have higher rates of cognitive impairment, and this study found that better cardiovascular fitness was associated with better structural integrity of brain white matter in middle-aged adults with HIV. Higher fitness was linked to greater density and coherence of multiple white matter tracts involved in motor control and other functions. Staying physically active may help protect brain structure and reduce the risk of cognitive decline in people living with HIV.

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Older men living with HIV who were switched to integrase inhibitor-based antiretroviral regimens had modestly lower body fat than those on older drug classes, but this difference largely disappeared after accounting for neighborhood-level socioeconomic status. Inflammatory and hormonal markers did not differ between the two drug groups. Socioeconomic factors, not just the specific antiretroviral regimen, are a major driver of body composition differences in older men with HIV.

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This study compared insulin metabolism in African American and non-Hispanic White people with obesity using three different testing methods. Contrary to findings from older intravenous glucose tests, African American participants were not more insulin resistant than White participants, and their after-meal insulin secretion and clearance were equivalent. The discrepancy with older studies appears to stem from methodological flaws in the intravenous glucose tolerance test, which exaggerates apparent racial differences.

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Researchers compared insulin sensitivity and insulin secretion in 15 people with obesity and sleep apnea versus 13 people with obesity but without sleep apnea, using detailed metabolic testing. Sleep apnea was associated with severe insulin resistance in muscle and fat tissue, but had no effect on how much insulin the pancreas secreted. This means sleep apnea causes a specific type of diabetes risk — insulin resistance rather than insulin deficiency — which has implications for how patients should be treated.

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This study measured how quickly free fatty acids (the building blocks released from body fat) move through the blood in lean people and people with obesity, and how this relates to insulin resistance in muscle. People with obesity cleared fatty acids from their blood faster than lean people, and faster clearance — not higher fatty acid levels — correlated with worse muscle insulin sensitivity. The rate at which cells extract fat from the blood, not just how much fat is circulating, determines cellular fat overload.

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An 8-month intensive lifestyle program delivered at the worksite produced 17% average weight loss and broad metabolic improvements in 18 people with obesity and type 2 diabetes. Improvements spanned blood sugar control, insulin sensitivity in multiple organs, heart-lung fitness, muscle strength, and liver fat — linked to changes in muscle energy metabolism and fat tissue remodeling. Providing the program at work substantially improved adherence and demonstrates that intensive lifestyle therapy is feasible and highly effective.

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The hearts of young adults with Barth syndrome extract and use more glucose but less fat than healthy hearts, a reversal of normal cardiac fuel preference, and these metabolic changes were directly linked to worse heart function. This study was the first to characterize myocardial fuel use in Barth syndrome using imaging techniques and found the altered metabolism reflects the underlying mitochondrial defect in this disease. Targeting cardiac metabolism may be a strategy for improving heart function in Barth syndrome.

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This pilot study tested whether resistance exercise combined with daily protein supplementation was safe and effective for young adults with Barth syndrome, a rare disease causing muscle weakness. After 12 weeks, the combined program increased muscle strength and quality of life and showed a trend toward increased lean mass, with no adverse events. The results support further investigation in larger studies to confirm the benefits of this approach in Barth syndrome.

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This study tested whether a single session of weight training before a meal improves blood sugar control in obese men with prediabetes. One workout reduced the blood sugar spike after eating by increasing insulin sensitivity and lowering the amount of glucose released into the bloodstream. This shows that resistance exercise has an immediate, measurable benefit on blood sugar metabolism even before any weight is lost.

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A randomized controlled trial tested whether vitamin D, conjugated linoleic acid (CLA), or both together could boost muscle protein synthesis in sedentary older adults. Neither supplement alone nor in combination had any effect on muscle protein building, either at rest or when stimulated by amino acids and insulin. These supplements, at the doses used, do not have muscle-building effects in older sedentary adults.

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This pilot study found that adolescents and young adults with Barth syndrome had lower rates of the amino acid arginine entering the bloodstream and being used by the body compared to healthy controls. Because arginine is a precursor for molecules involved in blood vessel function and energy metabolism, these abnormalities could contribute to the cardiovascular and exercise problems seen in the disease. The findings open new questions about how amino acid metabolism contributes to Barth syndrome pathology.

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Researchers examined why a single bout of resistance exercise lowers blood fat levels after a meal in obese men with prediabetes. Exercise reduced fat levels by cutting how much dietary and body-derived fat was packaged into triglyceride particles, while also boosting fat burning in muscle and fat tissue. This points to specific biological mechanisms that could explain how exercise reduces heart disease and diabetes risk.

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Children and young adults with Barth syndrome — a rare genetic condition affecting the heart and muscles — were studied to understand how their bodies use fuel during exercise. Their ability to burn fat during physical activity was severely impaired, and the body partially compensated by burning more glucose instead. These metabolic defects appear to be a core feature of the disease and help explain the exercise intolerance seen in these patients.

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This study tested whether the nerve-signaling pathway involving acetylcholine relays the effects of xenin-25, a gut hormone, on insulin and glucagon release in humans with prediabetes. Blocking acetylcholine receptors with atropine abolished the effect of xenin-25 on pancreatic polypeptide release but had no effect on insulin or glucagon, in contrast to findings in mice. Xenin-25 uses different signaling pathways in humans than in rodents to regulate hormone secretion.

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Young adults with Barth syndrome have substantially lower muscle strength, muscle mass, bone density, and exercise capacity than healthy peers. A 12-week resistance training program in three participants was safe, well-tolerated, and significantly increased muscle strength. These preliminary results support larger trials of resistance training in Barth syndrome.

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Adding extra whey protein to the diet during weight loss in middle-aged postmenopausal women with obesity slightly reduced early muscle loss, but this effect disappeared by the time 10% weight loss was reached, and muscle strength was unaffected by the extra protein. The overall muscle loss with diet-induced weight loss was small in both groups. High protein supplementation during calorie-restriction weight loss does not provide meaningful protection of muscle in this population.

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Exercise capacity in children and young adults with Barth syndrome is severely limited and, unlike healthy individuals, does not improve across childhood into adulthood. Cross-sectional and longitudinal data both showed that peak oxygen uptake remained stable and far below normal from childhood through young adulthood, with both heart and skeletal muscle function contributing to this limitation. This stable but persistently low exercise capacity underscores the need for therapies that address both cardiac and muscular defects in Barth syndrome.

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This study tested the common belief that leucine, an amino acid in protein, is solely responsible for triggering muscle protein synthesis after eating protein. When women consumed protein or an equivalent dose of leucine alone during controlled insulin conditions, only protein — not leucine alone — increased muscle protein synthesis. Leucine activates signaling pathways but is not sufficient by itself; other amino acids in protein are also needed to fully build muscle.

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Four young adults with Barth syndrome completed a 12-week cycling exercise program safely, with modest improvements in peak exercise capacity in three of four participants and improvements in some quality-of-life measures. Heart function and muscle oxygen use did not change significantly. Exercise training appears safe in Barth syndrome but produces smaller gains than typically seen in other heart or muscle conditions, suggesting the disease-specific metabolic defects limit the training response.

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When overweight people lost about 7% of their body weight through calorie restriction, exercise, or both, certain hormone levels shifted in ways that tracked closely with improvements in insulin sensitivity. Specifically, leptin and high-molecular-weight adiponectin decreased while pentraxin-3 increased, and together these changes explained most of the variation in insulin sensitivity improvements. Exercise added to calorie restriction had greater effects on leptin than either approach alone.

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Children and adults with Barth syndrome have impaired energy production in both their heart muscle and skeletal muscles, measured by the ratio of energy storage molecules and the speed of muscle energy recovery after exercise. These defects in cellular energy production were linked to lower exercise capacity but not to resting heart function. Impaired bioenergetics in both heart and skeletal muscle contribute to the exercise intolerance that is a hallmark of Barth syndrome.

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This study tested whether HIV infection blunts the metabolic improvements that usually come with weight loss, comparing women with and without HIV who lost 6-8% of their body weight through diet. Weight loss improved insulin sensitivity in fat tissue, liver, and muscle similarly in both HIV-positive and HIV-negative women, though HIV-positive women lost slightly more lean mass during weight loss. HIV infection does not prevent the metabolic benefits of moderate weight loss.

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Nearly half of patients sent home on intravenous nutrition through a central catheter developed a complication, and nearly a third had to have their catheter removed due to infection. The strongest independent predictors of infection-related catheter removal were use of blood thinners, having an ulcer or open wound, and having Medicare or Medicaid insurance. Patients with these risk factors need closer monitoring and targeted infection-prevention strategies.

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In women with obesity and type 2 diabetes during late pregnancy, the liver continued to produce glucose at high rates even during insulin infusion, and fat tissue was more resistant to insulin's fat-suppressing effect, compared to lean or obese women without diabetes. The mother's glucose and fat levels during insulin infusion were the strongest predictors of how large the baby was at birth. Maternal metabolic dysregulation during pregnancy directly influences fetal growth.

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Fish oil omega-3 fatty acid supplementation for six months changed the activity of multiple gene pathways in the skeletal muscle of older adults, with increases in genes supporting mitochondrial function and extracellular matrix organization and decreases in genes that break down muscle. The changes in individual gene expression were small, but they were coordinated across interconnected pathways. These transcriptional shifts may explain how omega-3 supplementation improves muscle mass and function in older people.

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Xenin-25, a gut-derived hormone, slows stomach emptying and reduces blood sugar after meals in people with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes, but these effects require sustained infusion of at least 90 minutes. The hormone also suppresses the incretin GLP-1 without changing insulin secretion, and nerve fibers in the stomach wall that carry the signal were identified. Xenin-25 controls gastric emptying through a neural pathway rather than by directly stimulating the pancreas.

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This study used a drug that mimics nerve signaling to test whether the autonomic nervous system regulates insulin and glucagon in humans with different glucose tolerance levels. The drug amplified gut hormone responses differently across groups but had no effect on insulin secretion or blood glucose in any group. Increasing peripheral nerve input to the pancreas boosts insulin secretion in mice but not in humans, highlighting important species differences in how the nervous system controls blood sugar.

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Losing 6-8% of body weight through calorie restriction alone, exercise alone, or both combined produced similar improvements in cardiovascular risk factors — including lower blood pressure, cholesterol, and blood glucose — regardless of which method was used. Only fitness improved in proportion to how much exercise was done. When the amount of weight lost is matched across methods, the cardiovascular benefits are largely equivalent.

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Eating a high-protein diet (1.2 g per kg per day) during weight loss in postmenopausal women with obesity reduced lean mass loss by about 45% compared to the standard recommended protein intake — but it also completely blocked the improvements in muscle insulin sensitivity and glucose uptake that weight loss normally produces. High protein intake also prevented beneficial changes in muscle oxidative stress and structural pathways. The protein content of a weight-loss diet matters: more protein preserves lean mass but appears to come at the cost of metabolic improvements.

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Eating protein impairs the ability of insulin to drive glucose into muscle cells, but this insulin-desensitizing effect is not caused by leucine activating the mTOR signaling pathway — even though both whey protein and leucine equally activated mTOR. Only whole protein, not leucine alone, reduced insulin-mediated glucose disposal. Protein intake after meals is a regulator of blood sugar, and its mechanism operates independently of the leucine-mTOR pathway.

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In overweight adults who lost 6-8% of body weight through calorie restriction alone, exercise alone, or both combined, the combination produced about twice the improvement in insulin sensitivity compared to either method alone. Calorie restriction alone also uniquely reduced a gut hormone called GLP-1, suggesting it may work partly through this pathway. Combining diet and exercise produces additive metabolic benefits beyond weight loss alone.

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A diabetes drug called sitagliptin, given for eight weeks to HIV-positive adults with impaired glucose tolerance, reduced blood glucose, improved insulin sensitivity, and lowered markers of systemic inflammation and immune activation compared to placebo. It also reduced inflammatory gene expression in fat tissue. This points to sitagliptin as a potentially useful treatment for both metabolic and inflammatory complications of HIV, warranting larger long-term trials.

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This review catalogued and evaluated 17 instruments used to measure workplace policies and physical environments that support or hinder physical activity and healthy eating. Most instruments lacked items about the social environment at work, and there were more tools covering physical activity than healthy eating. Better measurement tools that capture workplace social factors are needed to design and evaluate workplace health programs.

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Six months of fish oil omega-3 supplementation increased thigh muscle volume, grip strength, and lower- and upper-body strength in healthy adults aged 60-85 compared to a corn oil placebo. The benefits were seen in both men and women. Fish oil omega-3 supplementation is a practical strategy to slow the loss of muscle mass and strength that occurs with aging.

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Pregnant women with HIV taking antiretroviral therapy had lower levels of leucine oxidation than HIV-negative pregnant women, suggesting altered protein metabolism during pregnancy. Infants born to HIV-positive mothers also tended to have slightly reduced cardiac function, and lower maternal leucine levels were linked to this. The findings suggest antiretroviral therapy during pregnancy may affect maternal amino acid metabolism in ways that could influence infant cardiac development.

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One day of eating 30% more calories than needed did not raise daytime blood glucose or fat levels but did raise blood sugar and insulin levels during the night, while nighttime free fatty acid levels actually dropped. The next morning, insulin resistance was about 30% worse. A single episode of overeating disrupts overnight glucose regulation, and the mechanism does not appear to involve elevated fatty acids in the blood.

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Infusing the gut hormone xenin-25 slowed stomach emptying and reduced after-meal blood glucose in people with normal glucose tolerance, prediabetes, and type 2 diabetes equally, but only when the infusion lasted at least 90 minutes. The hormone worked by activating nerve pathways to the stomach rather than by directly stimulating insulin release. These findings suggest xenin-25 could be a target for therapies that slow glucose absorption after meals.

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Postmenopausal women were given estradiol, progesterone, or testosterone through skin patches and gels to test which sex hormone drives differences in blood triglyceride levels. Only estradiol reduced triglycerides — by about 30% — by speeding up the clearance of triglyceride-carrying particles from the bloodstream. This identifies estradiol as the primary sex hormone regulating triglyceride metabolism in women.

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Researchers compared muscle-building processes in younger women versus older women after menopause, then gave the older women different hormones to see which ones helped build muscle. Testosterone and progesterone both increased muscle growth by about 50% in postmenopausal women, but estradiol had no effect. This matters because it shows which hormones actually help prevent the muscle loss that naturally happens as women age, which could inform better treatments for maintaining strength and mobility in older women.

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In a large study comparing HIV-positive and HIV-negative adults with and without metabolic complications, having metabolic risk factors — not HIV infection — was the main driver of impaired heart relaxation (diastolic dysfunction). HIV infection was independently associated with worse heart pumping function, but did not worsen diastolic dysfunction beyond what metabolic complications alone caused. Monitoring heart function in anyone with metabolic risk factors, regardless of HIV status, is important for preventing cardiac complications.

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When the gut peptide xenin-25 is combined with another gut hormone called GIP, it amplifies the release of pancreatic polypeptide — an indirect marker of nerve input to the pancreas — similarly in people with normal glucose tolerance, prediabetes, and type 2 diabetes. Structural analysis of human pancreatic tissue showed that the receptor for xenin-25 is found on nerve fibers near the pancreas, not on insulin-producing cells directly. Xenin-25 acts through a neural relay to influence pancreatic function, not by directly stimulating islet cells.

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This pilot trial tested whether the diabetes drug pioglitazone or a combined exercise program could improve heart insulin sensitivity and diastolic function in HIV-positive adults with metabolic complications. Neither intervention produced a detectable improvement in heart metabolism or diastolic function, and post-hoc analysis showed that more than 100 participants would be needed to detect such an effect. Larger trials are needed before conclusions can be drawn about these interventions for HIV-related cardiac metabolic dysfunction.

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This study examined what happens to fat metabolism after just one day of eating 30% more calories than needed in overweight and obese men. A single day of overeating reduced liver insulin sensitivity and increased secretion of fat-carrying lipoprotein particles from the liver, even without changing overall fat in the blood. The findings show that acute caloric excess rapidly impairs liver metabolism before any weight gain occurs.