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Precision Medicine in Diabetes, Current Research and Future Perspectives

by

Roberto Franceschi

J. Pers. Med. 2022, 12(8), 1233; https://doi.org/10.3390/jpm12081233 - 28 Jul 2022

Cited by 3 | Viewed by 1402

Abstract

The prevalence of diabetes has tripled over the past 2 decades, and by 2050, it is estimated to affect 700 million adults [...] Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

Research

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Open AccessArticle

Genetic and Clinical Characterization of Patients with HNF1B-Related MODY in Croatia

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Maja Baretić

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Domagoj Caban

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Jadranka Sertić

J. Pers. Med. 2023, 13(7), 1063; https://doi.org/10.3390/jpm13071063 - 28 Jun 2023

Viewed by 487

Abstract

Background: Mutation of the gene encoding Hepatocyte Nuclear transcription Factor-1 Beta (HNF1B) causes a rare monogenetic subtype of Maturity-Onset Diabetes of the Young (MODY). HNF1B-related MODY results in the dysfunction of multiple organ systems. However, genetic analysis enables personalized medicine for patients and [...] Read more.

Background: Mutation of the gene encoding Hepatocyte Nuclear transcription Factor-1 Beta (HNF1B) causes a rare monogenetic subtype of Maturity-Onset Diabetes of the Young (MODY). HNF1B-related MODY results in the dysfunction of multiple organ systems. However, genetic analysis enables personalized medicine for patients and families. Aims: To understand the clinical characteristics and explore the gene mutations in Croatian patients. Methods: This was a retrospective observational study of individuals (and their relatives) who were, due to the clinical suspicion of MODY, referred to the Department of Laboratory Diagnostics at the University Hospital Centre Zagreb for genetic testing. Results: A total of 118 participants, 56% females, were screened. Seven patients (three females) from five families were identified to have HNF1B-related MODY. The median age at diagnosis was 31 (11–45) years, the median c-peptide was 0.8 (0.55–1.39) nmol/L, the median HbA1c was 9.1 (5.7–18.4)%, and the median BMI was 22.9 kg/m² (17–24.6). Patients had a variety of clinical manifestations; kidney disease was not as frequent as liver lesions, neuropsychiatric symptoms, hyperlipidemia, hyperuricemia, and hypomagnesemia. We identified two new pathogenic mutations (c.1006C > G protein p.His336Asp on exon 4 and c.1373T > G p protein Val458Gly on exon 7). Conclusions: In a study involving Croatian patients, new genetic (two previously unknown mutations) and clinical (diverse range of clinical presentations) aspects of HNF1B-related MODY were found. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

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Open AccessArticle

Family and Community Nurses as a Resource for the Inclusion of Youths with Type 1 Diabetes at School

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J. Pers. Med. 2023, 13(6), 981; https://doi.org/10.3390/jpm13060981 - 11 Jun 2023

Viewed by 838

Abstract

School nurses can facilitate the inclusion of students with type 1 diabetes (T1D) at school; this model has been widespread in some countries but not in Italy, which is due to the insufficient number of school nurses that are able to provide medical [...] Read more.

School nurses can facilitate the inclusion of students with type 1 diabetes (T1D) at school; this model has been widespread in some countries but not in Italy, which is due to the insufficient number of school nurses that are able to provide medical attention at all times. The National Recovery and Resilience Plan (PNRR) devised a series of aids and support for the reorganization of the Italian National Health System (NHS) through the creation of community houses in addition to family and community nurses (FCNs), who will operate in these structures to promote the integration of the various professional figures and community services. In this study, starting with the needs and suggestions of teachers (No. 79) and parents (No. 48) collected using a survey, we developed a new model for the inclusion of students at school where FCNs who have experience in pediatric T1D have the role of an educator, coordinator, and facilitator’ they cannot be on site and available all the time during school hours, so they must make many efforts to improve the school staff’s knowledge, intervene to offer training when requested, and solve new emerging problems. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

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Open AccessArticle

The Correlation between Metformin Use and Incident Dementia in Patients with New-Onset Diabetes Mellitus: A Population-Based Study

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J. Pers. Med. 2023, 13(5), 738; https://doi.org/10.3390/jpm13050738 - 26 Apr 2023

Viewed by 3277

Abstract

The evidence of metformin’s effect on dementia is conflicting. This study investigates the association between metformin use and the risk of dementia among patients with diabetes mellitus (DM). This study included patients with new-onset DM between 2002 and 2013. We divided the patients [...] Read more.

The evidence of metformin’s effect on dementia is conflicting. This study investigates the association between metformin use and the risk of dementia among patients with diabetes mellitus (DM). This study included patients with new-onset DM between 2002 and 2013. We divided the patients into patients who used metformin and patients who did not. Two models were used to assess metformin use: the cumulative defined daily dose (cDDD) of metformin use and the intensity of metformin use. This study with 3-year and 5-year follow-ups investigated the risk of dementia among patients with DM who used metformin. At the 3-year follow-up, patients who received cDDD < 300 had an odds ratio (OR) of developing dementia of 0.92 (95% confidence interval [CI] = 0.89–0.96); patients who used metformin at intensities <10 and 10–25 DDD/month had ORs of 0.92 (95% CI: 0.87–0.97) and 0.92 (95% CI: 0.85–1.00), respectively. Metformin use at cDDD 300–500 (OR = 0.80, 95% CI = 0.56–1.15) or >500 (OR = 1.48, 95% CI = 0.48–4.60) or at an intensity >25 DDD/month (OR = 0.84, 95% CI = 0.60–1.18) were not associated with an incident of dementia. There were similar results at the 5-year follow-up. Patients with a low intensity of metformin use had a lower risk of dementia. However, higher doses of metformin with higher intensity exhibited no protective role in dementia. Prospective clinical trials are warranted to evaluate the actual underlying mechanisms between metformin dosage and the risk of dementia. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

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Open AccessArticle

Prevalence of Cognitive Decline in Type 2 Diabetes Mellitus Patients: A Real-World Cross-Sectional Study in Mysuru, India

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Santhepete N. Manjula

J. Pers. Med. 2023, 13(3), 524; https://doi.org/10.3390/jpm13030524 - 15 Mar 2023

Viewed by 1220

Abstract

The goal of this research is to study the prevalence of cognitive impairment in diabetes mellitus (DM) patients and establish the necessity of detecting and treating it early in these patients. A cross-sectional study was conducted at a tertiary care hospital in Mysuru [...] Read more.

The goal of this research is to study the prevalence of cognitive impairment in diabetes mellitus (DM) patients and establish the necessity of detecting and treating it early in these patients. A cross-sectional study was conducted at a tertiary care hospital in Mysuru for 4 months examined diabetic patients (test) and nondiabetic subjects (control) for cognitive decline using the Montreal Cognitive Assessment (MoCA) tool. Cognitive functions such as visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation were assessed in both groups. The diabetic group showed a significantly lower total MoCA score than the non-diabetic group (18.99 ± 0.48 and 26.21 ± 0.46, respectively; p < 0.001). Assessment of scores in diabetic patients demonstrated the significant influence of age demographics on cognitive impairment (p-value < 0.001). Furthermore, a higher proportion of diabetic patients displayed cognitive impairment despite a higher score in a single subdomain, making it evident that diabetes is diverse and multifactorial in origin, where oxidative stress and inflammatory responses play a predominant role. This study suggested that the local T2DM population residing in Mysuru (India) has a high prevalence of cognitive impairment, evident from poor performance in almost all cognitive domains assessed by MoCA. Future studies could examine the generalizability of cognitive function findings in diabetic patients across diverse geographic regions and ethnic groups, as well as investigate interventions such as lifestyle modifications and medication to prevent or delay cognitive decline in those with diabetes. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

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Open AccessArticle

Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series

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J. Pers. Med. 2022, 12(10), 1613; https://doi.org/10.3390/jpm12101613 - 30 Sep 2022

Cited by 2 | Viewed by 943

Abstract

Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing [...] Read more.

Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing (NGS) panels provide a highly sensitive method even for rare forms. Methods: We investigated 28 pediatric subjects suspected for MODY-X, utilizing a 15-gene NGS panel for monogenic diabetes (MD). Results: NGS detected variants of uncertain significance (VUS), likely pathogenic or pathogenic for rarer subtypes of MODY, in six patients. We found variants in the wolframin gene (WFS1), traditionally not considered in MD genetic screening panels, in three patients; KCNJ11 gene mutation, typically responsible for neonatal diabetes and rarely causing isolated diabetes in adolescents; INS gene mutation; a variant in the HNF1B gene in a young male with diabetes on sulfonylurea treatment. Conclusion: In our cohort, the availability of an NGS panel for MD was determined for the correct identification of MD subtypes in six patients with MODY-X. Our study underlines how a precise diagnosis utilizing NGS may have an impact on the management of different forms of MODY and, thus, lead to a tailored treatment and enable genetic counselling of other family members. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

Open AccessArticle

Influence of Parental Health Locus of Control on Behavior, Self-Management and Metabolic Control, in Pediatric Patients with Type 1 Diabetes

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J. Pers. Med. 2022, 12(10), 1590; https://doi.org/10.3390/jpm12101590 - 27 Sep 2022

Cited by 2 | Viewed by 805

Abstract

Background: Precision medicine in type 1 diabetes (T1D) treatment considers context and environmental data to subclassify patients. Parental Health Locus of Control PHLOC) could influence behavior, self-management, and metabolic control of children with T1D. Methods: No. 135 pediatric patients with T1D (No. 57 [...] Read more.

Background: Precision medicine in type 1 diabetes (T1D) treatment considers context and environmental data to subclassify patients. Parental Health Locus of Control PHLOC) could influence behavior, self-management, and metabolic control of children with T1D. Methods: No. 135 pediatric patients with T1D (No. 57 with HbA1c ≤ 7.0%, “optimal” group, and No. 78 with >7.0%, “sub-optimal” group) were enrolled in the study. History, anthropometric and diabetes management data were collected, as well as caregiver’s data about socioeconomic status (SES). The PHLOC scale questionnaire and a semi-structured interview were administered. Results: Access to technology was lower in the “sub-optimal” group and, in particular, in the ethnic minority subgroup, only 8% used them. In the “sub-optimal” group ethnic minority status was higher (24%), the caregiver had a lower SES and showed lower internal HLOC. Conclusions: New care models have to be implemented to ensure equity in diabetes care and precision treatment, particularly for ethnic minority groups, because SES and external PHLOC are still an important barrier to “optimal” diabetes control. In the “sub-optimal” group, we have to implement strategies aimed at increasing self-efficacy, while in the “optimal” one, a personalised approach should be considered to facilitate the shifting of responsibilities within the family, avoiding psychological distress. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

Review

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Open AccessReview

Measures of Patient-Reported Expectations, Acceptance, and Satisfaction Using Automated Insulin Delivery Systems: A Review

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Francesco Maria Rosanio

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J. Pers. Med. 2023, 13(7), 1031; https://doi.org/10.3390/jpm13071031 - 22 Jun 2023

Viewed by 520

Abstract

In people with type 1 diabetes, Automated Insulin Delivery (AID) systems adjust insulin delivery in response to sensor glucose data and consist of three components: an insulin pump, a continuous glucose sensor, and an algorithm that determines insulin delivery. To date, all the [...] Read more.

In people with type 1 diabetes, Automated Insulin Delivery (AID) systems adjust insulin delivery in response to sensor glucose data and consist of three components: an insulin pump, a continuous glucose sensor, and an algorithm that determines insulin delivery. To date, all the available AID systems require users to announce carbohydrate intake and deliver meal boluses, as well as respond to system alarms. The use of AID devices both initially and over time may be influenced by a variety of psychological factors. Analysis of patient-related outcomes should be taken into account, while recruiting applicants for the systems who are motivated and have realistic expectations in order to prevent AID dropout. We report an up-to-date summary of the available measures and semi-structured interview content to assess AID expectations, acceptance, and satisfaction using the AID systems. In conclusion, we suggest, before and after starting using AID systems, performing a specific evaluation of the related psychological implications, using validated measures and semi-structured interviews, that allows diabetes care providers to tailor their education approach to the factors that concern the patient at that time; they can teach problem-solving skills and other behavioral strategies to support sustained use of the AID system. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

Open AccessReview

Optimal Prandial Timing of Insulin Bolus in Youths with Type 1 Diabetes: A Systematic Review

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Francesco Maria Rosanio

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Maria Loredana Marcovecchio

J. Pers. Med. 2022, 12(12), 2058; https://doi.org/10.3390/jpm12122058 - 13 Dec 2022

Cited by 1 | Viewed by 864

Abstract

The aim of this systematic review was to report the evidence on optimal prandial timing of insulin bolus in youths with type 1 diabetes. A systematic search was performed including studies published in the last 20 years (2002–2022). A PICOS framework was used [...] Read more.

The aim of this systematic review was to report the evidence on optimal prandial timing of insulin bolus in youths with type 1 diabetes. A systematic search was performed including studies published in the last 20 years (2002–2022). A PICOS framework was used in the selection process and evidence was assessed using the GRADE system. Up to one third of children and adolescents with type 1 diabetes injected rapid-acting insulin analogues after a meal. Moderate–high level quality studies showed that a pre-meal bolus compared with a bolus given at the start or after the meal was associated with a lower peak blood glucose after one to two hours, particularly after breakfast, as well as with reduced HbA1c, without any difference in the frequency of hypoglycemia. There were no differences related to the timing of bolus in total daily insulin and BMI, although these results were based on a single study. Data on individuals’ treatment satisfaction were limited but did not show any effect of timing of bolus on quality of life. In addition, post-prandial administration of fast-acting analogues was superior to rapid-acting analogues on post-prandial glycemia. There was no evidence for any difference in outcomes related to the timing of insulin bolus across age groups in the two studies. In conclusion, prandial insulin injected before a meal, particularly at breakfast, provides better post-prandial glycemia and HbA1c without increasing the risk of hypoglycemia, and without affecting total daily insulin dose and BMI. For young children who often have variable eating behaviors, fast-acting analogues administered at mealtime or post-meal could provide an additional advantage. Full article

(This article belongs to the Special Issue Diabetes Mellitus: Current Research and Future Perspectives)

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