Tag Archives: Metabolism

Milk May Lower T2D Risk in Patients With Lactose Intolerance

Diabetes News


Patients with lactose intolerance are usually advised to avoid milk. However, many still consume dairy products despite experiencing gastrointestinal symptoms. Surprisingly, this “unreasonable” strategy may have the benefit of reducing the risk for type 2 diabetes, as shown in a recent American study.

“At first glance, the statement of the study seems counterintuitive,” said Robert Wagner, MD, head of the Clinical Studies Center at the German Diabetes Center-Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. “However, lactose intolerance has different manifestations.” Less severely affected individuals often consume milk and tolerate discomfort such as bloating or abdominal pain. “It is precisely these individuals that the study clearly shows have a lower incidence of diabetes associated with milk consumption,” said Wagner.

Milk’s Heterogeneous Effect

The effect of milk consumption on diabetes, among other factors, has been repeatedly studied in nutritional studies, with sometimes heterogeneous results in different countries. The reason for this is presumed to be that in Asia, most people — 60%-100% — are lactose intolerant, whereas in Europe, only as much as 40% of the population has lactose intolerance.

The authors, led by Kai Luo, PhD, research fellow in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, did not mention lactose tolerance and intolerance in their paper in Nature Metabolism. Instead, they divided the study population into lactase-persistent and non-lactase-persistent participants.

“Not being lactase-persistent does not necessarily exclude the ability to consume a certain amount of lactose,” said Lonneke Janssen Duijghuijsen, PhD, a nutrition scientist at Wageningen University, Wageningen, the Netherlands. “Studies have shown that many individuals who lack lactase can still consume up to 12 g of lactose per day — equivalent to the amount in a large glass of milk — without experiencing intolerance symptoms.”

Gut Microbiome and Metabolites

Luo and his colleagues analyzed data from 12,653 participants in the Hispanic Community Health Study/Study of Latinos, an ongoing prospective cohort study involving adults with Hispanic backgrounds. It collects detailed information on nutrition and the occurrence of diseases.

The authors examined whether the study participants were lactase-persistent or non-lactase-persistent and how frequently they consumed milk. They also analyzed the gut microbiome and various metabolites in the blood over a median follow-up period of 6 years.

The data analysis showed that higher milk consumption in non-lactase-persistent participants — but not in lactase-persistent participants — is associated with about a 30% reduced risk for type 2 diabetes when socioeconomic, demographic, and behavioral factors are accounted for. Comparable results were obtained by Luo and his colleagues with data from the UK Biobank, which served as validation.

A higher milk consumption was associated not only with a lower diabetes risk in non-lactase-persistent individuals but also with a lower body mass index. “This could be one of the factors behind the diabetes protection,” said Wagner. “However, no formal mediation analyses were conducted in the study.”

Luo’s team primarily attributed the cause of the observed association between milk consumption and diabetes risk to the gut. Increased milk intake was also associated with changes in the gut microbiome. For example, there was an enrichment of Bifidobacterium, while Prevotella decreased. Changes were also observed in the circulating metabolites in the blood, such as an increase in indole-3-propionate and a decrease in branched-chain amino acids.

These metabolites, speculated the authors, could be more intensely produced by milk-associated bacteria and might be causally related to the association between milk consumption and reduced risk for type 2 diabetes in non-lactase-persistent individuals. “The authors have not been able to provide precise evidence of these mediators, but one possible mediator of these effects could be short-chain fatty acids, which can directly or indirectly influence appetite, insulin action, or liver fat beneficially,” said Wagner.

Bacteria in the Colon

For Janssen Duijghuijsen, the conclusion that milk consumption can influence the composition of the microbiome and thus the metabolic profile, especially in individuals without lactase persistence, is plausible.

“Individuals with lactase persistence efficiently digest lactose and absorb the resulting galactose and glucose molecules in the small intestine. In contrast, in non-lactase-persistent individuals, lactase is not expressed in the brush border of the small intestine. As a result, lactose remains undigested in the colon and can serve as an energy source for gut bacteria. This can influence the composition of the microbiome, which in turn can alter the concentration of circulating metabolites,” she said.

Janssen Duijghuijsen has investigated the effect of lactose intake on the microbiome. In a recently published study, she also showed that increasing lactose intake by non-lactase-persistent individuals leads to changes in the microbiome, including an increase in Bifidobacteria.

“In line with the current study, we also found a significant increase in fecal β-galactosidase activity. Given the close relationship between the composition of the gut microbiome and the metabolite profile, it is likely that changes in one can affect the other,” said Janssen Duijghuijsen.

Nutritional Recommendations

The nutrition scientist warned against concluding that milk consumption can protect against type 2 diabetes in non-lactase-persistent individuals, however. “The study suggests a statistical association between milk consumption, certain metabolites, and the frequency of type 2 diabetes. These associations do not provide definitive evidence of a causal relationship,” she said. Any dietary recommendations cannot be derived from the study; much more research is needed for that.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.



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Analysis of remission and relapse rate of type 2 diabetes mellitus in Japan

Diabetes News


The phenomenon of improvement of glucose to levels in a normal range and cessation of the need for medication can occur in some patients diagnosed with type 2 diabetes who are provided with lifestyle therapy, temporary pharmacotherapy, bariatric surgery, or combinations of these treatments.

However, this phenomenon is not yet fully understood in routine care settings, and many factors remain to be clarified. Moreover, since there are differences in insulin secretion and resistance between East Asian and Western populations, the natural history of diabetes seems to differ widely between Western populations and East Asians.

Therefore, these concerns lead Dr. Kazuya Fujihara and colleagues to investigate the incidence/one year relapse from remission and associated factors in patients with type 2 diabetes. In the Diabetes, Obesity and Metabolism paper, the authors addressed these research questions using a database of specialists’ clinics.

They analyzed the data of Japan Diabetes Clinical Data Management Study Group (JDDM) which is one of the largest cohorts of Japanese people with type 2 diabetes. They tracked the information on 48,320 people with diabetes in Japan. In one arm of the study, they calculated remission rates per 1000 person-years. The authors reported that the median follow-up was 5.3 years. During the study period, 3,677 remissions occurred.

The overall incidence of remissions per 1,000 person-years was 10.5 that was similar to 9.7 in the United Kingdom. In addition, those with HbA1c levels of 48 to 53 mmol/mol (6.5% to 6.9%), those taking no glucose-lowering drugs at baseline, and those with a ≥10% body mass index (BMI) reduction in 1 year, it was 27.8, 21.7 and 48.2, respectively.

Male sex, shorter duration, lower baseline HbA1c, higher baseline BMI, higher BMI reduction at 1 year, and no glucose-lowering drugs at baseline were significantly associated with remission. Similar results were obtained with maintenance of remission over 1 year as an outcome. In another arm of the study, the investigators revealed the factors that predicted relapse from remission in 1 year.

Among 3,677 individuals who entered remission, two-thirds (2,490) relapsed from remission within 1 year. Longer duration of diabetes, lower BMI at baseline, and lower BMI reduction at 1 year were significantly associated with relapse. Commenting on the significance of their findings.

Compared to Westerners, Asians have higher insulin sensitivity and a lower acute insulin response. In addition, Asians have a much lower obesity level than Westerners, and the pathogenesis of diabetes mellitus is very different between the two. Therefore, the relationships of baseline BMI and BMI reduction with remission and relapse may be greater in East Asian than in Western populations, implying ethnic differences in returning from overt hyperglycemia to nearly normal glucose levels.”


Hirohito Sone, Niigata University

While the findings of these analytical study are impressive and provide new insight on remission in patients with type 2 diabetes should be, the authors noted that “present study is an observational study and does not show a cause and effect relationship, and that future intervention studies with lifestyle and/or medication will be needed to confirm how many people actually achieve remission and how long the state of remission lasts in real world setting”.

Source:

Journal reference:

Fujihara, K., et al. (2023) Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73). Diabetes, Obesity and Metabolism. doi.org/10.1111/dom.15100.



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Study suggests COVID-19 can cause diabetes

Diabetes News
Study: New-Onset Diabetes and COVID-19: Evidence from a Global Clinical Registry. Image Credit: ADragan / Shutterstock


The authors of a new study under review at Nature Portfolio and currently posted to the Research Square preprint* server showed the clinical possibility that the coronavirus disease 2019 (COVID-19) heightens the risk of developing diabetes mellitus (DM), supporting diabetes screening in those infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 

Study: New-Onset Diabetes and COVID-19: Evidence from a Global Clinical Registry. Image Credit: ADragan / ShutterstockStudy: New-Onset Diabetes and COVID-19: Evidence from a Global Clinical Registry. Image Credit: ADragan / Shutterstock

Background

An increasing body of evidence suggests that COVID-19 is associated with new diabetes diagnoses. However, it is unclear whether COVID-19 detects pre-existing diabetes or induces new-onset diabetes.

Although previous research reported high blood-sugar levels and metabolic consequences resulting from pre-existing diabetes following COVID-19 hospitalization, studies correlating the disease to new-onset DM are scarce.

COVID-19 has been shown to exacerbate pre-existing diabetes. This likely occurs because COVID-19 is associated with low-grade inflammation, which may initiate or worsen insulin resistance. In addition, numerous studies have also demonstrated that SARS-CoV-2 can infest and multiply within insulin-producing pancreatic beta-cells, thus impairing insulin synthesis and secretion. 

However, whether SARS-CoV-2 can cause clinically meaningful changes in glucose metabolism remains unclear. Nevertheless, it may be possible to find an answer by characterizing the clinical symptoms of COVID-19-related diabetes and by determining the period between the onset of hyperglycemia and that of the infection.

It is imperative to establish a causal relationship between COVID-19 and diabetes since both diseases are prevalent throughout the world. Furthermore, establishing a causal relationship will have significant implications for diagnosis, management, public health, and scientific research. Despite this, it remains unclear whether the association between COVID-19 and diabetes results from indirect health consequences of the former, such as – a higher rate of detection of pre-existing diseases, or whether the causative virus (SARS-CoV-2) directly precipitates hyperglycemia. 

Owing to the higher rate of pre-existing disease detection in the COVID era, newly diagnosed diabetes may be explained both during and after an episode of infectious exposure.

The study

This study investigated the possibility that COVID-19 may trigger new-onset diabetes and its associated symptoms by examining average blood-glucose levels at the time of diabetes presentation against a global clinical registry.

A global COVID-19-related diabetes (CoviDIAB) registry was established to determine whether COVID-19 can acutely induce diabetes and its clinical symptoms. The CoviDIAB registry collects information regarding “newly diagnosed diabetes” and “severe metabolic complications associated with pre-existing diabetes” resulting from COVID-19. 

Individuals with a fasting blood glucose of 126 mg/dL or above or non-fasting blood glucose of 200 mg/dL or above, with no prior diabetes history, and those who had never been on glucose-lowering medications, and with their glycated hemoglobin (HbA1c) levels below the diabetic range (< 6.5%) at presentation were categorized as new-onset diabetes. Here, the researchers examined cases of newly diagnosed diabetes that occurred within four weeks of COVID-19 confirmation. In addition, the HbA1c data were evaluated at the time of diabetes detection to rule out pre-existing hyperglycemia and to confirm the association with SARS-CoV-2 infection.

The findings

Data on 537 eligible newly diagnosed diabetes cases was entered from 61 hospitals in 25 countries between 2020-2022. COVID-19 patients with newly diagnosed diabetes at presentation had HbA1c levels above the diagnostic range, suggesting pre-existing hyperglycemia.

In cases with new-onset hyperglycemia after the SARS-CoV-2 infection, individuals displayed glycemic levels above the diagnostic thresholds, although their HbA1c levels remained within the non-diabetic range. The results showed that 22% of newly diagnosed patients with documented HbA1c levels had recently acquired diabetes.

The most common diabetes subtype among adults was type 2 DM (59%), and the “not yet known” subtype (41%). Two newly diagnosed cases of type 1 DM were recorded among children. After COVID-19 resolution, hyperglycemia persisted in 39 of 89 patients (45%) with newly diagnosed diabetes.

For 28 of these individuals, follow-up data beyond three months was collected, demonstrating that five of them were in remission from diabetes, while 23 (82%) remained diabetic. 

The findings suggested that COVID-19 causes clinically significant changes in glucose metabolism. Although this study does not prove that SARS-CoV-2 causes diabetes, it strongly suggests that the virus may impose a diabetogenic aftermath. 

Further, type 2 DM was the predominant subtype among COVID-19 participants with newly diagnosed diabetes. Thus, type 2 DM likely accounts for most newly diagnosed diabetes cases associated with the post-acute phase of the SARS-CoV-2 infection.

This study confirms this phenomenon across diverse geographical locations and ethnicities by incorporating clinical observations from 25 countries. 

Numerous areas for improvement have been identified in this study, including inherent heterogeneity in clinical practice and the judgment of contributing physicians. 

Conclusion

The results of this study suggest that COVID-19 likely has a diabetogenic effect. Thus, individuals exposed to SARS-CoV-2 infection must be screened for diabetes. Further research is necessary to confirm the mechanisms through which the virus interferes with glucose metabolism.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.



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