Mixed-Lineage Leukaemia Gene Regulates Glucose-Sensitive Gene Expression and Insulin Secretion in Pancreatic Beta Cells.

The escalating prevalence of diabetes mellitus underscores the need for a comprehensive understanding of pancreatic beta cell function. Interest in glucose effectiveness has prompted the exploration of novel regulatory factors. The myeloid/lymphoid or mixed-lineage leukaemia gene (MLL) is widely recognised for its role in leukemogenesis and nuclear regulatory mechanisms through its histone methyltransferase activity in active chromatin. However, its function within pancreatic endocrine tissues remains elusive. Herein, we unveil a novel role of MLL in glucose metabolism and insulin secretion. MLL knockdown in ßHC-9 pancreatic beta cells diminished insulin secretion in response to glucose loading, paralleled by the downregulation of the glucose-sensitive genes SLC2a1 and SLC2a2. Similar observations were made in MLL heterozygous knockout mice (MLL+/-), which exhibited impaired glucose tolerance and reduced insulin secretion without morphological anomalies in pancreatic endocrine cells. The reduction in insulin secretion was independent of changes in beta cell mass or insulin granule morphology, suggesting the regulatory role of MLL in glucose-sensitive gene expression. The current results suggest that MLL interacts with circadian-related complexes to modulate the expression of glucose transporter genes, thereby regulating glucose sensing and insulin secretion. Our findings shed light on insulin secretion control, providing potential avenues for therapeutics against diabetes.

Assessment of factors associated with improved glycemic control after switching from intermittently scanned to real-time continuous glucose monitoring in Japanese patients with type 1 diabetes.

The advantages of real-time continuous glucose monitoring (rtCGM) over intermittently scanned CGM (isCGM) reportedly include lower glycated hemoglobin (HbA1c) levels as well as reduced glycemic variability. However, there have been few studies of the effect of switching from isCGM to rtCGM on glycemic control, as well as the specific factors underlying any observed improvements. To that end, all patients with type 1 diabetes mellitus who used the DEXCOM rtCGM device (Terumo Corporation, Tokyo, Japan) at our institution were reviewed, and 16 individuals with type 1 diabetes who switched from isCGM to rtCGM were investigated. The patients' HbA1c decreased in 75% of the cases (p = 0.02). On the other hand, GMI increased in 75% of the cases (p = 0.01). Intriguingly, the percentage of time below range and coefficient of variation were significantly improved with rtCGM compared to isCGM (2.9% vs. 7.6%, p = 0.016 and 35% vs. 40%, p = 0.0019, respectively). We also found that the discrepancy between HbA1c and GMI among users of isCGM was a key indicator that improved when switching to rtCGM. If discrepancies are observed between HbA1c and GMI when using isCGM, switching to rtCGM should be considered for improving glycemic control.

A case of insulinoma-induced hypoglycemia managed by Dexcom G4 Platinum.

This report details the case of a 41-year-old woman who was diagnosed with insulinoma. As the patient developed severe life-threatening hypoglycemia, we introduced Dexcom G4 Platinum (DG4P), a modern continuous glucose-monitoring system (CGM). The algorithm of the sensor glucose (SG) values of CGM is based on patients with diabThis report details the case of a 41-year-old woman who was diagnosed with insulinoma. As the patient developed severe life-threatening hypoglycemia, we introduced Dexcom G4 Platinum (DG4P), a modern continuous glucose-monitoring system (CGM). The algorithm of the sensor glucose (SG) values of CGM is based on patients with diabetes; therefore, we evaluated the accuracy of DG4P in this patient. The mean absolute relative differences and absolute differences between SG of DG4P and self-monitoring of blood sugar values were 10.8%±8.3% and 6.8±5.7 mg/dL, respectively, in the hypoglycemic region, which verifies DG4P's accuracy. DG4P was found to be useful for monitoring hypoglycemia not only in patients with diabetes but also in those with insulinoma.etes; therefore, we evaluated the accuracy of DG4P in this patient. The mean absolute relative differences and absolute differences between SG of DG4P and self-monitoring of blood sugar values were 10.8%±8.3% and 6.8±5.7 mg/dL, respectively, in the hypoglycemic region, which verifies DG4P's accuracy. DG4P was found to be useful for monitoring hypoglycemia not only in patients with diabetes but also in those with insulinoma.

Maternal hypothyroidism is associated with M-opsin developmental delay.

Thyroid hormones are critical for the development of opsins involved in color vision. Hypothyroid mice show delayed M-opsin development and expanded distribution of S-opsin on the retina. However, the effects of maternal hypothyroidism on opsin development remain unknown. This study investigates the effects of congenital central hypothyroidism and maternal hypothyroidism on opsin development in thyrotropin-releasing hormone knockout (TRH-/-) mice. We examined the mRNA expression and protein distribution of S/M-opsin on postnatal days (P)12 and 17, as well as mRNA expression of type 2 and 3 iodothyronine deiodinase (DIO2 and DIO3, respectively) in the retina and type 1 iodothyronine deiodinase (DIO1) in the liver at P12 in TRH+/- mice born to TRH+/- or TRH-/- dams, and conducted S/M-opsin analysis in TRH+/+ or TRH-/- mice born to TRH+/- dams at P12, P17, and P30. M-opsin expression was lower in TRH+/- mice born to TRH-/- dams than in those born to TRH+/- dams, whereas S-opsin expression did not significantly differ between them. DIO1, DIO2, and DIO3 mRNA expression levels were not significantly different between the two groups; therefore, thyroid function in peripheral tissues in the pups was similar. S/M-opsin expression did not significantly differ between the TRH+/+ and TRH-/- mice born to TRH+/- dams on any postnatal day. These results demonstrate that maternal hypothyroidism causes M-opsin developmental delay during the early developmental stages of neonatal mice, and TRH-/- mice, a model of congenital central hypothyroidism, born to a euthyroid dam do not have delayed opsin development.

Development and preliminary validation of a machine learning system for thyroid dysfunction diagnosis based on routine laboratory tests.

Background: Approximately 2.4 million patients in Japan would benefit from treatment for thyroid disease, including Graves' disease and Hashimoto's disease. However, only 450,000 of them are receiving treatment, and many patients with thyroid dysfunction remain largely overlooked. In this retrospective study, we aimed to develop and conduct preliminary testing on a machine learning method for screening patients with hyperthyroidism and hypothyroidism who would benefit from prompt medical treatment. Methods: We collected electronic medical records and medical checkup data from four hospitals in Japan. We applied four machine learning algorithms to construct classification models to distinguish patients with hyperthyroidism and hypothyroidism from control subjects using routine laboratory tests. Performance evaluation metrics such as sensitivity, specificity, and the area under receiver operating characteristic (AUROC) were obtained. Techniques such as feature importance were further applied to understand the contribution of each feature to the machine learning output. Results: The results of cross-validation and external evaluation indicated that we achieved high classification accuracies (AUROC = 93.8% for hyperthyroidism model and AUROC = 90.9% for hypothyroidism model). Serum creatinine (S-Cr), mean corpuscular volume (MCV), and total cholesterol were the three features that were most strongly correlated with the hyperthyroidism model, and S-Cr, lactic acid dehydrogenase (LDH), and total cholesterol were correlated with the hypothyroidism model. Conclusions: We demonstrated the potential of machine learning approaches for diagnosing the presence of thyroid dysfunction from routine laboratory tests. Further validation, including prospective clinical studies, is necessary prior to application of our method in the clinic.

Casual C peptide index: Predicting the subsequent need for insulin therapy in outpatients with type 2 diabetes under primary care.

BACKGROUND: Evaluation of residual beta cell function is indispensable in patients with type 2 diabetes as it informs not only diagnoses but also appropriate treatment modalities. However, there is a lack of convenient biomarkers for residual beta cell function. Therefore, we evaluated endogenous insulin level as a biomarker in outpatients who were being treated with insulin therapy and in patients who were introduced to insulin therapy after 4 years. METHODS: Data of 174 outpatients with type 2 diabetes (50% male) whose glycemia was moderately controlled (glycated A1c 7.3% [5.2%-14.8%]) were reviewed. Twenty patients whose estimated glomerular filtration rate was lower than 30 ml/min/1.73 m2 were excluded from the evaluation of endogenous insulin level with both casual C-peptide index (C-CPI) and urinary C-peptide/creatinine ratio (determined at any time, generally 1-2 h after breakfast). Patients were stratified based on the provision of insulin therapy. RESULTS: C-CPI and UCPCR were significantly lower in the insulin-treated patients than in the insulin-untreated patients (0.9 vs. 2.2, p < 0.0001; 24.7 vs. 75.5, p = 0.0003, respectively). Moreover, C-CPI were significantly lower in the insulin-requiring patients for 4 years than in the insulin-unrequiring patients (1.0 vs. 1.7, p = 0.0184). The multivariate logistic regression analysis revealed that both indicators of insulin secretion influenced the requirement for insulin therapy, but C-CPI could serve as the most convenient and useful biomarker for not only current insulin therapy requirements (p = 0.0002) but also the subsequent requirement for insulin therapy (p = 0.0008). CONCLUSIONS: C-CPI could be determined easily, and it was found to be a more practical marker for outpatients; therefore, our findings would have critical implications for primary care.

Resolvin E3 ameliorates high-fat diet-induced insulin resistance via the phosphatidylinositol-3-kinase/Akt signaling pathway in adipocytes.

Obesity-associated type 2 diabetes mellitus is associated with the development of insulin resistance. Among several metabolites, resolvins that are metabolites of eicosapentaenoic acid have been shown to exert insulin-sensitizing effects; however, the role of resolvin E3 (RvE3) in glucose metabolism has not been studied. In this study, the effect of RvE3 on glucose metabolism in mice with high-fat diet-induced obesity and 3T3L1 adipocytes was studied. C57BL/6 mice fed a high-fat diet were administered RvE3, for which insulin tolerance, oral glucose tolerance tests, and the homeostasis model assessment of insulin resistance, were performed. RvE3 treatment significantly improved insulin sensitivity and glucose tolerance and regulated protein kinase B (Akt) phosphorylation in the adipose tissue. Moreover, RvE3 treatment enhanced the insulin-stimulated glucose transporter 4 (Glut4) translocation, glucose uptake, phosphatidylinositol-3-kinase (PI3K) activity, and Akt phosphorylation in 3T3L1 adipocytes, whereas a PI3K inhibitor inhibited the enhanced insulin-stimulated glucose uptake induced by RvE3. These findings indicate that RvE3 likely improves insulin sensitivity, resulting in the upregulation of glucose uptake in adipocytes by activating the PI3K/Akt signaling pathways. Collectively, the findings of this study show that RvE3 may play a role in glucose homeostasis and could be used as a potential therapeutic target for developing treatments for obesity-associated diabetes.

Superior Mesenteric Artery Syndrome Accompanied by Acute-onset Type 1 Diabetes Complicated with Graves' Disease.

A 35-year-old man experienced general fatigue and could not eat solid food because of nausea and vomiting. His weight abruptly decreased from 49 to 45 kg after 2 weeks. A detailed examination indicated superior mesenteric artery syndrome (SMAS) accompanied by acute-onset type 1 diabetes complicated by Graves' disease, referred to as autoimmune polyglandular syndrome type 3A (APS3A). Although SMAS has a good prognosis, some cases require emergency surgery, especially when complicated by gastric perforation. In our case, APS3A and SMAS developed rapidly and at approximately the same time, resulting in a cycle of mutual exacerbation.

The Hypothalamic Paraventricular Nucleus Is the Center of the Hypothalamic-Pituitary-Thyroid Axis for Regulating Thyroid Hormone Levels.

Background: Thyrotropin-releasing hormone (TRH) was the first hypothalamic hormone isolated that stimulates pituitary thyrotropin (TSH) secretion. TRH was also later found to be a stimulator of pituitary prolactin and distributed throughout the brain, gastrointestinal tract, and pancreatic ß cells. We previously reported the development of TRH null mice (conventional TRHKO), which exhibit characteristic tertiary hypothyroidism and impaired glucose tolerance due to insufficient insulin secretion. Although in the past five decades many investigators, us included, have attempted to determine the hypothalamic nucleus responsible for the hypothalamic-pituitary-thyroid (HPT) axis, it remained obscure because of the broad expression of TRH. Methods: To determine the hypothalamic region functionally responsible for the HPT axis, we established paraventricular nucleus (PVN)-specific TRH knockout (PVN-TRHKO) mice by mating Trh floxed mice and single-minded homolog 1 (Sim1)-Cre transgenic mice. We originally confirmed that most Sim1 was expressed in the PVN using Sim1-Cre/tdTomato mice. Results: These PVN-TRHKO mice exhibited tertiary hypothyroidism similar to conventional TRHKO mice; however, they did not show the impaired glucose tolerance observed in the latter, suggesting that TRH from non-PVN sources is essential for glucose regulation. In addition, a severe reduction in prolactin expression was observed in the pituitary of PVN-TRHKO mice compared with that in TRHKO mice. Conclusions: These findings are conclusive evidence that the PVN is the center of the HPT axis for regulation of serum levels of thyroid hormones and that the serum TSH levels are not decreased in tertiary hypothyroidism. We also noted that TRH from the PVN regulated prolactin, whereas TRH from non-PVN sources regulated glucose metabolism.

Pitfalls of intermittent continuous glucose monitoring in patients with steroid diabetes.

Only a few studies of continuous glucose monitoring (CGM) in patients with steroid diabetes have been published. Therefore, we investigated all patients with type 2 diabetes (n = 121) and steroid diabetes (n = 40) who used the FreeStyle Libre Pro® device (Abbott Japan) at Gunma University Hospital between 2017 and 2019. Glycated hemoglobin (HbA1c), mean sensor glucose (SG), and glucose management indicator values were similar in both groups. However, the indices for glycemic variabilities, expressed as standard deviations and percent coefficients of variation, were higher in patients with steroid diabetes than in those with type 2 diabetes. The associations between HbA1c, mean SG, and time in range (TIR) when glucose values were 70-180, <70, or >180 mg/dL were assessed using Pearson's product-moment correlation coefficient, which demonstrated good correlations in both patient groups. However, patients with steroid diabetes had a higher SG and lower TIR than did counterparts with type 2 diabetes who had similar HbA1c levels. To examine the effect of prednisolone on CGM data, we divided patients with steroid diabetes into 2 subgroups according to prednisolone dose (≤5 and >5 mg), and found that the dose of this steroid impacted the associations between HbA1c and CGM data, mean SG, and TIR. In summary, our data highlight the importance of cautiously interpreting CGM data and the optimal HbA1c level in patients with steroid diabetes to prevent diabetes-related complications. Further analyses using other CGM devices are necessary to further validate our findings.

The Optimal "Time in Range" and "Time below Range" are Difficult to Coordinate in Patients with Type 1 Diabetes.

Achieving the optimal glucose level time in range (TIR), as recently proposed by the "International Consensus on Time in Range," is challenging. We retrospectively analyzed data from 192 patients, including 58 with type 1 diabetes, using the FreeStyle Libre Pro system. This device was used by physicians for continuous glucose monitoring (CGM) and for making therapeutic decisions based on unbiased data, as the patients were blinded to their blood glucose levels during monitoring. The desired 70% TIR among patients with type 2 diabetes corresponded to an HbA1c of 7.7%. Importantly, however, a 70% TIR for patients with type 1 diabetes corresponded to an HbA1c of 6.9%, which diverged markedly from the HbA1c of 7.9% that corresponded to the desired 4% time below range (TBR). Moreover, these dissociations were observed more in patients with type 1 diabetes with a higher % coefficient of variation (> 36%). Hence, while the TIR is strongly correlated with HbA1c, it is difficult to coordinate with the TBR in Japanese patients with type 1 diabetes. As these metrics (which are critical indicators in clinical practice) are rapidly gaining popularity globally, including in Japan, our data strongly support the cautious use of new CGM metrics such as TIR and TBR/time above range, and emphasize the importance of individualized treatment in achieving the optimal TIR and TBR, especially in patients with type 1 diabetes.

Overexpressed exocyst complex component 3-like 1 spontaneously induces apoptosis.

Exocyst complex component 3-like 1 (EXOC3L1), which regulates insulin secretion, is ubiquitously present in heart, lung, liver, spleen, kidney, muscle, cerebellum, pituitary, adrenal grand, and pancreatic islets. Its deduced amino acid sequence has 31% identity and 53% similarity with Sec6, so they are considered isoforms. Since Sec6 suppresses apoptosis via HSP27, we investigated the involvement of EXOC3L1 expression in apoptosis. We found that overexpressed EXOC3L1 in Chinese hamster ovary cells significantly reduced cultured cell numbers. It also significantly increased apoptotic DNA ladder, caspase 3 activity, and cleavage of caspase 3 compared with the control. Thus, although Sec6 reduces apoptosis by increasing HSP27 phosphorylation, overexpressed EXOC3L1 alone can spontaneously induce apoptosis without apoptotic stimulators or inducers.

TBC1D8B, a GTPase-activating protein, is a novel apoptosis inducer.

Overexpressed TBC1D8B, a GTPase-activating protein, significantly reduced cultured HCT116 human colon cancer cell number. We tested N-terminal TBC1D8B, which is identical to wild type TBC1D8B from amino acid positions 1 to 427 and possesses a modified sequence from position 428 to 435 (ECGGLFLL) because of the introduction of a premature stop codon at position 436 to narrow down the minimum requirement element. The N-terminal TBC1D8B contains two GRAM domains but not the TBC domain essential for Rab-GTPase activity. The N-terminal TBC1D8B overexpression significantly reduced the cultured HCT116 cell number. When we tested C-terminal TBC1D8B, containing the portion of TBC1D8B absent in the N-terminal TBC1D8B, the cell number reduction was not observed. The N-terminal TBC1D8B overexpression significantly increased the coronin 1B expression and reduced the phosphorylation of serine 51 in eIF2α, respective markers of apoptosis and cell death/survival. Also, caspase 3 and poly ADP-ribose polymerase increased cleavage in suspended cells overexpressing the N-terminal TBC1D8B. Taken together, it is not the TBC domain for Rab-GTPase activity, but amino acids 1 to 435, including the two GRAM domains, that is enough for TBC1D8B to cause spontaneous apoptosis. TBC1D8B could be a potential anticancer therapeutic molecule.

SFPQ associated with a co-activator for PPARγ, HELZ2, regulates key nuclear factors for adipocyte differentiation.

We recently isolated a novel co-activator of peroxisome proliferator-activated receptor γ, helicase with zinc finger 2 (HELZ2). HELZ2 null mice were resistant to diet-induced obesity and NAFFL/NASH, and HELZ2 was phosphorylated at tyrosine residues. In order to find a factor related to HELZ2, we analyzed products co-immunoprecipitated with phosphorylated HELZ2 by mass spectrometry analyses. We identified proline- and glutamine-rich (SFPQ) as a protein associating with tyrosine-phosphorylated HELZ2. The knockdown of SFPQ in 3T3-L1 cells downregulated mRNA levels of transcription factors including Krox20, Cebpß, and Cebpδ: key factors for early-stage adipocyte differentiation. In addition, knockdown of SFPQ inhibited 3T3-L1 cell differentiation to mature adipocytes. These findings demonstrated that SFPQ associating with HELZ2 is an important novel transcriptional regulator of adipocyte differentiation.

Free triiodothyronine /free thyroxine ratio as an index of deiodinase type 1 and 2 activities negatively correlates with casual serum insulin levels in patients with type 2 diabetes mellitus.

Free triiodothyronine/free thyroxine (FT3/FT4) ratio is considered as an index of the activities of iodothyronine deiodinase types 1 and 2 (DIO1 and DIO2, respectively) and is reportedly associated with insulin resistance in euthyroid adults. Euthyroid women with polycystic ovary syndrome accompanied with insulin resistance have lesser deiodinase activities. Correspondingly, the serum insulin level in a fasted condition positively correlates with the FT3/FT4 ratio, and insulin depletion decreases the DIO2 activity in mice. Selected genetic variants in DIO1 are also associated with insulin resistance measures. Therefore, if insulin positively regulates DIO1 and DIO2, the FT3/FT4 ratio should decrease under impaired insulin action, and the casual insulin level and FT3/FT4 ratio should be negatively correlated. To evaluate this hypothesis, we conducted a single-center retrospective study between 2018 and 2021. All participants visited the selected hospitals monthly for type 2 diabetes mellitus treatment and casual plasma glucose and HbA1c level measurements. Furthermore, their casual serum insulin levels were measured annually. Meanwhile, we excluded patients treated with insulin injection. Ultimately, we evaluated 71 patients, which all exhibited euthyroid conditions. The FT3/FT4 ratio was independently associated with thyroid-stimulating hormone, casual plasma glucose, and casual insulin levels. In terms of the regression coefficients of the univariate linear regression analysis, the FT3/FT4 ratio negatively correlated with the casual serum insulin levels. Therefore, the risk of FT3/FT4 ratio underestimation should be considered when diagnosing Graves' disease, which is often accompanied with insulin resistance.

Influence of the stage of emergency declaration due to the coronavirus disease 2019 outbreak on plasma glucose control of patients with diabetes mellitus in the Saku region of Japan.

Objective: Because patients with diabetes mellitus (DM) were forced to stay indoors during the state of emergency, resulting in stress and a lack of physical activity, concerns about their glycemic control were raised. Patients and Methods: The 165 patients' glycated hemoglobin (HbA1c) levels were compared during the following periods: the 4 months that were selected as a representative condition 1 year before the COVID-19 pandemic (May 2018, March 2019, June 2019, and July 2019) and the latter 3 months as a 1-year follow-up during the COVID-19 pandemic (May 2019, March 2020, June 2020, and July 2020). Results: The patients' HbA1c levels were 7.32 ± 1.23, 7.44 ± 1.20, 7.16 ± 1.06, 7.01 ± 1.05, 7.23 ± 1.06, 7.45 ± 1.18, 7.15 ± 10.7, and 7.11 ± 1.17 in May 2018, March 2019, June 2019, July 2019, May 2019, March 2020, June 2020, and July 2020, respectively (expressed as mean ± standard deviation). Conclusion: The analysis showed that HbA1c levels did not worsen during the self-restraint period.

Angiotensin receptor blockers significantly reduce hemoglobin level in patients with type 2 diabetes mellitus not suffered chronic cardiac failure and chronic kidney disease.

Anemia due to angiotensin receptor blocker (ARB) therapy has been previously reported in patients with diabetes mellitus with glomerular filtration rates of <60 mL min-1/1.73 m2. However, whether Japanese patients with type 2 diabetes mellitus (T2DM) receiving ARB therapy for chronic cardiac failure and chronic kidney disease develop reduced hemoglobin (Hb) levels has not been elucidated. Thus, this cross-sectional study was conducted, and Hb levels were compared between patients with T2DM with and without ARB administration. No significant difference in the prescribed proportion of antidiabetic medicines such as biguanide, sodium glucose co-transporter 2 inhibitors, and α-glucosidase inhibitors was found between the group treated with ARBs and the group without ARBs. Thus, we considered that the effects of antidiabetic medicines on the results were minimum. In this study, the Hb levels of patients who received ARBs (13.8 ± 1.7 g/dL) were significantly lower than those of patients without ARBs (14.9 ± 1.35 g/dL) (p = 0.034). The difference between this study and a previous study relies on eGFR levels. Thus, the eGFR levels of the patients in this study and the previous study were above 60 and below 60 mL min-1/1.73 m2, respectively. Despite those differences, both studies showed that the use of ARBs was associated with a decrease in Hb levels in patients with T2DM. Thus, the evaluation of glycated Hb levels should be focused on whether ARBs are prescribed for patients with T2DM.

Late-onset non-islet cell tumor hypoglycemia: A case report.

BACKGROUND: Hypoglycemia due to non-insulin-producing tumors is referred to as non-islet cell tumor hypoglycemia (NICTH). As NICTH is a rare lesion, the natural course of NICTH is not well understood. We report a case of NICTH that was observed 30 years before the onset of hypoglycemia. CASE SUMMARY: A 50-year-old man was diagnosed with an abnormal right chest shadow during a routine X-ray examination, but no further examination was undertaken because the lesion appeared benign. Thirty years after the tumor discovery, the patient was admitted to the hospital with symptoms of severe hypoglycemia, which was diagnosed as NICTH based on a complete examination. The tumor was resected and found to be a solitary fibrous mass (15.6 cm × 13.7 cm × 10.4 cm); thereafter, the patient's blood glucose levels normalized and he completely recovered. CONCLUSION: NICTH can have an acute onset, even if the tumor has been present and asymptomatic over a long time period.

In patients with type 2 diabetes the presence of Hashimoto's thyroiditis reduces the beneficial effect of dipeptidyl peptidase-4 inhibitor on plasma glucose control.

In this study, we compared the efficacy of a dipeptidyl peptidase-4 inhibitor (DPP4i) to improve glucose control in patients with type 2 diabetes mellitus (T2DM) with or without Hashimoto's thyroiditis (HT). First, we compared the change in glycated hemoglobin (HbA1c) between the hypothyroid condition (before levothyroxine sodium hydrate [LT4] treatment) and euthyroid condition (after LT4 treatment when patients had achieved euthyroidism for at least six months) in patients with T2DM and HT. Next, we compared the change in HbA1c levels before and six months of DPP4i treatment in patients with T2DM with and without HT. In hypothyroid condition the change in HbA1c after six months of DPP4i treatment was 0.13% ± 0.86%. The change in HbA1c levels from when patients first achieved euthyroidism to after six months in the euthyroid condition was 0.26% ± 0.90%. DPP4i efficacy in patients with T2DM and HT was reduced compared to patients with T2DM but without HT (-0.40 ± 0.90 vs. -0.99 ± 0.5, p = 0.0032). These data suggest that hypothyroidism does not impact on DPP4i efficacy. However, the effect of DPP4i in patients with T2DM and HT was reduced compared to that in T2DM patients without HT. An estimation of thyroid function before prescribing DPP4i may be useful tool for predicting the efficacy of DPP4i, allowing the ruling out complications from HT.

Differences in the effects of Kenyan, Tanzanian, and Ethiopian coffee intake on interstitial glucose levels measured by FreeStyle Libre: A pilot case study.

BACKGROUND: Although generally considered part of a healthy diet, coffee consumption has been suspected to be associated with elevated epinephrine levels and increasing insulin resistance. OBJECTIVES: We studied the effects of the intake of 3 different types of coffee (Tanzanian, Ethiopian, and Kenyan) on postprandial interstitial glucose levels. METHOD: Interstitial glucose levels were measured every 15 minutes using the FreeStyle Libre glucose monitoring system (Abbott Diabetes Care Ltd, Witney, United Kingdom) in each individual after drinking coffee compared with when not consuming coffee. RESULTS: Unlike Tanzanian and Ethiopian coffees, Kenyan coffee suppressed the increase of postprandial interstitial glucose levels. Kenyan coffee beans contain less anhydrous caffeine and more chlorogenic acid than Tanzanian and Ethiopian coffee beans. These findings may explain the different effects of these coffee types on postprandial interstitial glucose levels. Furthermore, Kenyan coffee beans inhibited α-glucosidase activity, which may partially explain why Kenyan coffee reduces postprandial interstitial glucose levels. CONCLUSIONS: Coffee is widely consumed as a beverage worldwide, and our findings suggest that patients with diabetes mellitus may benefit from drinking Kenyan coffee because of its ability to reduce postprandial interstitial glucose levels. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).