Beta cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial

Roncero-Ramos, Irene; Gutiérrez-Mariscal, Francisco M.; Gómez-Delgado, Francisco; Villasanta‐Gonzalez, Alejandro; Torres-Peña, José D.; Cruz-Ares, Silvia de la; Rangel‐Zúñiga, Oriol A.; Luque, Raúl M; Ordovás, José M.; Delgado-Lista, Javier; Pérez‐Martínez, Pablo; Camargo, Antonio; Alcalá‐Díaz, Juan F.

doi:10.1016/j.trsl.2021.07.001

Cited by 13 publications

(21 citation statements)

References 48 publications

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“…Although previous studies have suggested that impairment in β-cell function predisposes the risk-allele carriers of the TCF7L2 variants to the progression of T2DM [ 8 , 9 ], the dysfunction in β-cell may be due to the insulin resistance that is more pronounced in healthy T-allele risk carriers [ 10 , 11 ]. There is evidence that participants with a family history of diabetes and genetic background of T2DM responded differentially to dietary and pharmacological treatment [ 65 , 66 ]. Regarding the metformin treatment, in participants with a new diagnosis of T2DM, insulin resistance decreased more among T-allele carriers.…”

Section: Discussionmentioning

confidence: 99%

“…However, this response became less efficacious among participants with the progression of the disease [ 65 ]. In addition, the dietary intervention had little effect on the prevention and delay in initiating glucose-lowering treatment in subjects with a family history of T2DM and those with high hepatic insulin resistance and β-cell dysfunction [ 66 ]. Moreover, in observational studies, the effect of fatty acids (both diet and plasma) on the relationship between TCF7L2 and glycemic parameters has been more studied [ 51 , 53 , 57 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…First, the target population in randomized trials were overweight and obese subjects who were predisposed to insulin resistance and T2DM. As mentioned above, the difference in response to treatment was reported between the TCF7L2 risk allele and the non-risk allele in the early but not in the late stage of diabetes [ 65 , 66 ]. Second, the influence of TCF7L2 on glycemic parameters can be modified by weight loss.…”

Section: Discussionmentioning

confidence: 99%

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Effect of TCF7L2 on the relationship between lifestyle factors and glycemic parameters: a systematic review

Hosseinpour-Niazi

Mirmiran

Hosseini

et al. 2022

Nutr J

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Background Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors. Methods A systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021. Results Thirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status. Conclusion The modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory. PROSPERO registration number CRD42020196327

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Effect of TCF7L2 on the relationship between lifestyle factors and glycemic parameters: a systematic review

Hosseinpour-Niazi

Mirmiran

Hosseini

et al. 2022

Nutr J

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“…1 was subsequently divided into two sections. [18][19][20][21][22][23][24] Section 1A lists the 4 trials with newly diagnosed T2D and no caloric restriction. Section 1B lists the 3 trials with newly diagnosed T2D and mild caloric restriction.…”

Section: Article Identification and Data Extractionmentioning

confidence: 99%

“…No trials were conducted in an African country. In fact, enrolment of people of African descent was described only in the two studies conducted in Barbados (24,27). These studies were small with 10 and 25 participants, respectively.…”

Section: Participant Characteristics: Country Race/ethnicity and Gendermentioning

confidence: 99%

A Scoping Review of Trials Designed to Achieve Remission of Type 2 Diabetes with Lifestyle Intervention Alone: Implications for Sub-Saharan Africa

Karera¹,

Wentzel²,

Ishimwe³

et al. 2023

DMSO

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According to the International Diabetes Federation, sub-Saharan Africa is experiencing the highest anticipate increase in the prevalence of type 2 diabetes (T2D) in the world and has the highest percent of people living with T2D who are undiagnosed. Therefore, diagnosis and treatment need prioritization. However, pharmacological hypoglycemics are often unavailable and bariatric surgery is not an option. Therefore, the ability to induce T2D remission through lifestyle intervention alone (LSI-alone) needs assessment. This scoping review evaluated trials designed to induce T2D remission by LSI-alone. PubMed, Embase, Cochrane, and CINAHL databases were searched for trials designed to induce T2D remission through LSI-alone. Of the 928 identified, 63 duplicates were removed. With abstract review, 727 irrelevant articles were excluded. After full-text review, 112 inappropriate articles were removed. The remaining 26 articles described 16 trials. These trials were published between 1984 and 2021 and were conducted in 10 countries, none of which were in Africa. Remission rates varied across trials. Predictors of remission were 10% weight loss and higher BMI, lower A1C and shorter T2D duration at enrollment. However, LSI-alone regimens for newly diagnosed and established T2D were very different. In newly diagnosed T2D, LSI-alone were relatively low-cost and focused on exercise and dietary counseling with or without calorie restriction (~1500 kcal/d). Presumably due to differences in cost, LSI-alone trials in newly diagnosed T2D had higher enrollments and longer duration. For established T2D trials, the focus was on arduous phased dietary interventions; phase 1: low-calorie meal replacement (<1000 kcal/day); phase 2: food re-introduction; phase 3: weight maintenance. In short, LSI-alone can induce remission in both newly diagnosed and established T2D. To demonstrate efficacy in Africa, initial trials could focus on newly diagnosed T2D. Insight gained could provide proof of concept and a foundation in Africa on which successful studies of LSI-alone in established T2D could be built.

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Remission of type 2 diabetes: always more questions, but enough answers for action

Rothberg,

Lean,

Laferrère

2024

Diabetologia

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The concept of type 2 diabetes remission is evolving rapidly, and gaining wide public and professional interest, following demonstration that with substantial intentional weight loss almost nine in ten people with type 2 diabetes can reduce their HbA1c level below the diagnostic criterion (48 mmol/mol [6.5%]) without glucose-lowering medications, and improve all features of the metabolic syndrome. Pursuing nomoglycaemia with older drugs was dangerous because of the risk of side effects and hypoglycaemia, so the conventional treatment target was an HbA1c concentration of 53 mmol/mol (7%), meaning that diabetes was still present and allowing disease progression. Newer agents may achieve a normal HbA1c safely and, by analogy with treatments that send cancers or inflammatory diseases into remission, this might also be considered remission. However, although modern glucagon-like peptide-1 receptor agonists and related medications are highly effective for weight loss and glycaemic improvement, and generally safe, many people do not want to take drugs indefinitely, and their cost means that they are not available across much of the world. Therefore, there are strong reasons to explore and research dietary approaches for the treatment of type 2 diabetes. All interventions that achieve sustained weight loss of >10–15 kg improve HbA1c, potentially resulting in remission if sufficient beta cell capacity can be preserved or restored, which occurs with loss of the ectopic fat in liver and pancreas that is found with type 2 diabetes. Remission is most likely with type 2 diabetes of short duration, lower HbA1c and a low requirement for glucose-lowering medications. Relapse is likely with weight regain and among those with a poor beta cell reserve. On current evidence, effective weight management should be provided to all people with type 2 diabetes as soon as possible after diagnosis (or even earlier, at the stage of prediabetes, defined in Europe, Australasia, Canada [and most of the world] as ≥42 and <48 mmol/mol [≥6.0 and <6.5%], and in the USA as HbA1c ≥39 and <48 mmol/mol [≥5.7 and <6.5%]). Raising awareness among people with type 2 diabetes and their healthcare providers that remission is possible will enable earlier intervention. Weight loss of >10 kg and remission lasting 1–2 years may also delay vascular complications, although more evidence is needed. The greatest challenge for research is to improve long-term weight loss maintenance, defining cost-effective approaches tailored to the preferences and needs of people living with type 2 diabetes. Graphical Abstract

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Beta cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial

Abstract: cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial.,

Cited by 13 publications

References 48 publications

Effect of TCF7L2 on the relationship between lifestyle factors and glycemic parameters: a systematic review

Effect of TCF7L2 on the relationship between lifestyle factors and glycemic parameters: a systematic review

A Scoping Review of Trials Designed to Achieve Remission of Type 2 Diabetes with Lifestyle Intervention Alone: Implications for Sub-Saharan Africa

Remission of type 2 diabetes: always more questions, but enough answers for action

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