Advancements in the field of diabetes care continue to emerge, making it challenging for clinicians to stay up to date with the latest findings. This article highlights recent evidence on managing and lowering risk for type 2 diabetes.

EVEN AN HOUR'S WALK A WEEK LOWERS RISK IN TYPE 2 DIABETES

The prevalence of type 2 diabetes in adults and children is rising. Approximately 37 million people in America have diabetes, of whom 90% to 95% have type 2 diabetes.^[1] Furthermore, type 2 diabetes is associated with multiple complications including neuropathy, retinopathy and nephropathy, as well as macrovascular complications, decreased quality of life and mortality. In a new cohort study, investigators evaluated more than 500,000 people from the UK Biobank aged 37 to 82 years to determine the relationship between leisure-time physical activity and risk of incident retinopathy, neuropathy and nephropathy.^[2]

Researchers found that performing any level of leisure-time physical activity reduced the risk for neuropathy and nephropathy in individuals with type 2 diabetes, by between one fifth and one third, although the impact on retinopathy was weaker. The research, based on data from more than 18.000 participants, suggests that the minimal level of self-reported activity to reduce the risk for both neuropathy and nephropathy may be the equivalent of less than 1.5 hours of walking per week.

The results are "encouraging and reassuring for both physicians and patients," lead author Frederik P.B. Kristensen, MSc, PhD student, Department of Clinical Epidemiology, Aarhus University, Denmark, told Medscape Medical News. "Our findings are particularly promising for neuropathy since currently, no disease-modifying treatment exists and there are limited preventive strategies available." Kristensen highlighted that "most diabetes research has focused on all-cause mortality and macrovascular complications. In the current study, we also found the same pattern for microvascular complications: Even small amounts of physical activity will benefit your health status." The minimal level of activity they identified, he said, is also an "achievable" goal "for most type 2 diabetes patients."

Kristensen added, however, that the study was limited by excluding individuals with limited mobility and those living in temporary accommodation or care homes. And prospective studies are required to determine the dose-response relationship between total, not just leisure-time, activity — ideally measured objectively — and risk for microvascular complications, he observed.

The research was published recently in Diabetes Care.

Impact of Exercise on Microvascular Complications in T2D Has Been Uncertain

The authors point out that microvascular complications — such as nerve damage (neuropathy), kidney problems (nephropathy), and eye complications (retinopathy) — occur in more than 50% of individuals with type 2 diabetes and have a "substantial impact" on quality of life, on top of the impact of macrovascular complications (such as cardiovascular disease), disability, and mortality.

Although physical activity is seen as a "cornerstone in the multifactorial management of type 2 diabetes because of its beneficial effects on metabolic risk factors," the impact on microvascular complications is "uncertain" and the evidence is limited and "conflicting."

The researchers therefore sought to examine the dose-response association, including the minimal effective level, between leisure-time physical activity and neuropathy, nephropathy, and retinopathy. They conducted a cohort study of individuals aged 37 to 82 years from the UK Biobank who had type 2 diabetes, which was identified using the Eastwood algorithm and/or an A1c ≥ 48 mmol/mol (6.5%). Individuals with type 1 diabetes or gestational diabetes were excluded, as were those with major disabling somatic disorders, neurodegenerative diseases, and mental disorders, among others. Leisure-time physical activity was based on the self-reported frequency, duration, and types of physical activities and was combined to calculate the total leisure time activity in MET-hours per week. Using the American Diabetes Association/World Health Organization recommendations of 150-300 minutes of moderate to vigorous leisure-time physical activity per week, the researchers determined the recommended moderate activity level to be 150 minutes, (equivalent to 2.5 hours, or 7.5 MET-hours per week).

In all, 18,092 individuals with type 2 diabetes were included in the analysis, of whom 37% were women. The mean age was 60 years. Ten percent of participants performed no leisure-time physical activity, 38% performed activity below the threshold for moderate activity, 20% performed at the recommended level, and 32% were more active. Those performing no physical activity were more likely to be women, to be younger, to have a higher body mass index, and to have a greater average A1c, as well as have a more unfavorable sociodemographic and behavioral profile.

Over a median follow-up of 12.1 years, 3.7% of the participants were diagnosed with neuropathy, 10.2% with nephropathy, and 11.7% with retinopathy, equating to an incidence per 1000 person-years of 3.5, 9,8, and 11.4, respectively. The researchers found that any level of physical activity was associated with an approximate reduction in the risk for neuropathy and nephropathy. Multivariate analysis indicated that, compared with no physical activity, activity below the recommended level was associated with an adjusted hazard ratio (aHR) for neuropathy of 0.71, whereas the aHR for activity at the recommended level was 0.73 and that for activity above the recommended level was 0.67.

The aHR for nephropathy compared with no physical activity was 0.79 for activity below the recommended level, 0.80 for activity at the recommended level, and 0.80 for activity above the recommended level. The association between physical activity and retinopathy was weaker, however, at aHRs of 0.91, 0.91, and 0.98 for activity below, at, and above the recommended level, respectively. The researchers suggest that this lower association could be due to differences in the etiology of the different forms of microvascular complications. Hyperglycemia is the key driver in the development of retinopathy, they note, whereas other metabolic risk factors, such as obesity, insulin resistance, inflammation, dyslipidemia, and hypertension, play a role in neuropathy and nephropathy. The associations were also less pronounced in women.

Kristensen said that this is "an important area that needs to be addressed. While different rates between men and women regarding incidence of type 2 diabetes, metabolic risk factors, complications, and the initiation of, and adherence to, therapy have been found," he continued, "the exact mechanisms remain unclear. We need a further understanding of sex-differences in metabolic regulation, as well as in material living conditions, social and psychological factors, and access to healthcare, which may influence the risk of complications." Kristensen added, "Sex differences may be present in more areas than we are aware [of]."

APPLE CIDER VINEGAR, FENUGREEK BEST HERBAL REMEDIES FOR T2D

Considerable progress has been made in the development of treatments for type 2 diabetes. However, a cure is yet to be discovered. Traditional medicines have been used throughout time, across the globe. While thousands of herbal therapies are available for the treatment of type 2 diabetes, few have undergone scientific testing.^[3] A new systematic review and network meta-analysis explored the impact of herbal preparations on the glycemic levels of patients with type 2 diabetes. The review included 44 randomized clinical trials with more than 3000 participants using 6 herbal remedies: apple cider vinegar, cinnamon, curcumin, fenugreek seeds, ginger, and saffron.^[4]

The study found that apple cider vinegar and fenugreek seeds were the most effective at reducing fasting blood glucose and A1c levels compared with 4 other popular herbal remedies for type 2 diabetes. Apple cider vinegar, fenugreek seeds, curcumin (turmeric), and cinnamon resulted in statistically significant reductions in fasting blood glucose compared with the control groups in the clinical trials. Out of all the remedies, the authors found apple cider vinegar to be the most effective for lowering fasting blood glucose levels. The review also found that apple cider vinegar and fenugreek seeds had a statistically significant effect on reducing A1c compared with the control groups. The authors found the herbal remedies made no difference to insulin level or homeostatic model assessment for insulin resistance (HOMA-IR). 

The results are published online in Diabetes & Metabolic Syndrome: Clinical Research & Reviews. The authors said they hoped the review would help medical professionals and people with type 2 diabetes understand the effectiveness of different herbal remedies and consider incorporating these remedies into standard care.^[4] 

"Some people use curcumin, some use ginger, some use apple cider, but it's not clear which is better," said Shiv Mudgal, PhD, corresponding author of the paper and an associate professor in nursing at the All India Institute of Medical Sciences in Deoghar, India.  "We thought it would be nice to get some idea about how they work and how they compete with each other," said Subodh Kumar, MD, the first author and an associate professor in pharmacology at the All India Institute of Medical Sciences in Deoghar, India. 

They wanted to understand how the herbal remedies worked by including insulin level and HOMA-IR as measurable outcomes but found nothing conclusive. Instead, they speculated that the effect of apple cider vinegar and fenugreek seeds on blood glucose and A1c could be related to delayed gastric emptying, among other mechanisms. 

However, the results should be interpreted with caution, said Kumar. Apple cider vinegar had three clinical trials to back the finding, and fenugreek seeds had four studies supporting the results — fewer than the other included remedies. The authors also identified risks of bias from the randomization process and the allocation concealment process in several of the included trials. 

Most of the studies included only short follow-up periods, meaning that the long-term effects of using these herbal remedies to help manage type 2 diabetes remain unclear. The six herbal remedies included in the study were chosen out of dozens of popular complementary medicines for the strength and number of clinical trials backing their use. 

The limited number included in the review is a drawback, according to Merlin Willcox, DPhil, a clinical lecturer in general practice at the University of Southampton, United Kingdom, who was not involved in the research. "It means they've left out stuff that's potentially effective," Willcox told Medscape Medical News. Willcox, who has co-authored a review of herbal remedies for glycemic control in type 2 diabetes,^[5] said he was surprised that apple cider vinegar came out on top in this analysis. His review concluded that aloe vera leaf gel, psyllium fiber, and fenugreek seeds appeared to be the most effective at reducing A1c compared with the control groups of the included trials, out of 18 plant-based remedies. 

There were no adverse effects associated with the herbal remedies, according to Mudgal. However, the evidence for the herbal remedies included in their review also lacked substantial follow-up periods assessing their long-term effects. "You need to look at the evidence for each individual remedy; it's not just about what plant it is, but it's about what preparation, what dose. All of that comes into play," Willcox said. 

Up to 3.6 million people use herbal remedies to manage type 2 diabetes in the United States, according to a 2014 study cited by the review authors.^[6] The number is much higher elsewhere: As many as two thirds of patients with diabetes in India and Saudi Arabia incorporate herbal remedies to help manage symptoms, whereas about half of patients with diabetes in the United Kingdom use herbal medicines.

Experts warn of the risks associated with using herbal medicines to complement traditional therapies. "I caution my patients about dietary supplements and herbals because of the lack of high-quality data demonstrating efficacy and safety," Katherine H. Saunders, MD, DABOM, co-founder of Intellihealth and clinical assistant professor of medicine at Weill Cornell Medicine, told Medscape Medical News. 

For Willcox, the risks relate to where patients get their information from. Many patients with type 2 diabetes are too scared to talk to their clinician about herbal medicines. "They think their doctor is going to be negative or dismissive," Willcox said. "So patients are getting their information from family and friends or from the internet, which is not necessarily the most reliable, evidence-based source of information." 

BOTH TOO MUCH AND NOT ENOUGH SLEEP RAISES T2D RISK

Historically, behaviors such as smoking, drinking alcohol, nutrition and exercise have been the primary focus of type 2 diabetes studies. In recent years, there has been an increasing interest in the impact of sleep on disease risk. Indeed, evidence suggests that various aspects of sleep patterns are associated with type 2 diabetes.^[7]

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data for 5561 participants aged 40 to 75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights' data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1341 type 2 diabetes, and the mean sleep duration was 8.3 hours
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes vs 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8
• The association between sleep duration and diabetes was not significant

IN PRACTICE:

The results "support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption," write the authors.

"These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation," they add.

SOURCE:

The research was led by Jeroen D. Albers, MSc, Department of Social Medicine, Maastricht University, Maastricht, the Netherlands, and published in Sleep Health on August 10. It is an analysis of The Maastricht Study.^[7]

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are "plausible causal paths between sleep duration and type 2 in both directions," the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

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