Diet and Physical Activity as Determinants of Continuously Measured Glucose Levels in Persons at High Risk of Type 2 Diabetes

We examined how dietary and physical activity behaviors influence fluctuations in blood glucose levels over a seven-day period in people at high risk for diabetes. Twenty-eight participants underwent a mixed meal tolerance test to assess glucose homeostasis at baseline. Subsequently, they wore an accelerometer to assess movement behaviors, recorded their dietary intakes through a mobile phone application, and wore a flash glucose monitoring device that measured glucose levels every 15 min for seven days. Generalized estimating equation models were used to assess the associations of metabolic and lifestyle risk factors with glycemic variability. Higher BMI, amount of body fat, and selected markers of hyperglycemia and insulin resistance from the meal tolerance test were associated with higher mean glucose levels during the seven days. Moderate- to vigorous-intensity physical activity and polyunsaturated fat intake were independently associated with less variation in glucose levels (CV%). Higher protein and polyunsaturated fatty acid intakes were associated with more time-in-range. In contrast, higher carbohydrate intake was associated with less time-in-range. Our findings suggest that dietary composition (a higher intake of polyunsaturated fat and protein and lower intake of carbohydrates) and moderate-to-vigorous physical activity may reduce fluctuations in glucose levels in persons at high risk of diabetes.

Spontanhypoglykämien: Eine diagnostische Herausforderung

Zusammenfassung Anamnese Die Vorstellung einer 59-jährigen Frau erfolgte zur endokrinologischen Abklärung rezidivierender Spontanhypoglykämien. Die Beschwerden waren stets nach Kohlenhydrataufnahme regredient. Aufgrund eines klassischen adrenogenitalen Syndroms erhielt die Patientin seit jungen Jahren eine Substitutionstherapie mit Hydrocortison. Untersuchung Die Patientin präsentierte sich in einem altersentsprechenden Allgemein- und leicht übergewichtigen Ernährungszustand. Der Blutzucker lag zum Aufnahmezeitpunkt bei 87 mg/dl. Weiterhin konnten unter Substitution mit retardiertem Hydrocortison ein unauffälliges Cortisol sowie adrenokortikotropes Hormon (ACTH) nachgewiesen werden. Im Mixed-Meal-Tolerance-Test (MMTT, standardisierter Frühstückstest) zeigte sich keine reaktive Hypoglykämie. Im anschließenden 72-Stunden-Hungerversuch trat nach 36 Stunden eine symptomatische Hypoglykämie auf. Bei einem Blutzucker von 46 mg/dl (Referenzbereich: 74–106) fand sich ein vermindertes Insulin. Auffällig waren jedoch ein niedriges Cortisol sowie ein deutlich erhöhtes ACTH, hinweisend auf eine Unterversorgung mit Hydrocortison zum Zeitpunkt der Hypoglykämie. Therapie und Verlauf Aufgrund der vermuteten therapeutischen Lücke wurde mit der Patientin eine Dosiserhöhung des morgendlichen retardierten Hydrocortisons besprochen. Da dies keinen klinischen Erfolg hatte, wurde die Applikationsform auf morgens und abends geändert. Folgerung Die vorliegende Kasuistik demonstriert, dass nicht nur ein endogener Hyperinsulinismus ursächlich für Spontanhypoglykämien sein kann, sondern ebenfalls eine fehlerhafte Gegenregulation zu symptomatischen Unterzuckerungen führen kann. Der MMTT sowie der 72-Stunden-Hungerversuch sollten zur Diagnostik angewendet werden. Hierbei ist darauf zu achten, dass in der Hypoglykämie eine unmittelbare Hormonanalytik erfolgt. Durch das Verhältnis von Insulin, C-Peptid sowie Proinsulin zum Blutzucker und anhand der Konstellation der kontrainsulinären Hormone wie Cortisol, ACTH, Wachstumshormon, Insulin-like growth factor 1 (IGF-1) sowie der Katecholamine kann eine Aussage über die Ätiologie der Hypoglykämie getroffen werden.

Satisfactory Rapid Response to Xultophy Associated with Meal Tolerance Test (MTT) by Carbohydrate Loading

The case is a 69-year-old male patient with Type 2 Diabetes Mellitus (T2DM) for 21 years. His diabetic control was not so satisfactory, and his HbA1c value increased in spring 2021. Then, he started Xultophy (IDegLira), which includes a fixed ratio of two agents of basal degludec and liraglutide. Just after providing Xultophy, the daily profile of blood glucose decreased from 179-400 mg/dL to 112-171 mg/dL, with remarkable clinical efficacy. He usually takes 80g of carbohydrates in breakfast, and the meal tolerance test (MTT) was challenged. As carbohydrate loading was given 100-75-50-0%, postprandial hyperglycemia at 60-min showed 277-219-159-133 mg/dL, respectively.

Potential of an Enzyme Mixture of Glucose Oxidase, Glucosyl Transferase, and Fructosyl Transferase as an Antidiabetic Medicine

An enzyme mixture (EM) of glucose oxidase, glucosyl transferase, and fructosyl transferase can regulate glucose absorption into the body by converting carbohydrates in food to indigestible oligosaccharides. We evaluated the antidiabetic effects of repeated oral administration of EM in db/db mice. Seven-week-old db/db mice were divided into control, voglibose, and EM groups. Drugs were administered orally mixed with limited feed for one month. Glucose levels were measured every week. A meal tolerance test was conducted after overnight fasting, before the mice were sacrificed. There were no differences in body weight or food intake between the groups. EM treatment reduced blood glucose levels compared with those in the control group. Blood glucose levels during the meal tolerance test were significantly lower in the EM group than those in the control group. A significant decrease in triglyceride level and a tendency for decreased low-density lipoprotein were observed in the EM group compared with in the control group. The Bacteroidetes-to-Firmicutes ratio was higher in the EM group than that in the control group. EM may be useful for people at risk of hyperglycemia or diabetes who need to safely regulate their blood glucose levels. EM may also improve lipid and gut microbiota profiles.

Effects of mixed meal tolerance test on gastric emptying, glucose and lipid homeostasis in obese nonhuman primates

Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.

A comparison of meal tolerance test and oral glucose tolerance test for predicting insulin therapy in patients with gestational diabetes

Aims: To identify factors predicting a need for insulin therapy in gestational diabetes mellitus (GDM) by comparing plasma glucose (PG) levels in a 75-g oral glucose tolerance test (75-g OGTT) with those in a 500-kcal meal tolerance test (MTT) containing 75 g of carbohydrate. Subjects and methods: The MTT was performed in 61 patients who diagnosed with GDM by a 75-g OGTT (age, 33.2 ± 4.5 years; prepregnancy body mass index, 22.6 ± 4.7 kg/m2; number of gestational weeks, 25.1 ± 6.4 weeks). PG and serum insulin levels were measured before the meal and up to 180 min after the meal. The insulin secretion capacity and resistance index were calculated. Results: PG levels increased from 86.8 ± 8.8 mg/dL at fasting to 132.7 ± 20.1 mg/dL at 30 min, and 137.8 ± 27.7 mg/dL at 60 min after MTT in the 35 patients with needed insulin therapy; these levels were significantly higher than those in the 26 patients, who only needed diet therapy. The patients with needed insulin therapy had significantly higher fasting PG levels in the 75-g OGTT, PG levels at fasting and 30 min after the MTT, and homeostasis model assessment of insulin resistance (HOMA-IR), and a significantly lower disposition index (DI) and insulin index than patients treated by diet alone. Receiver operating characteristic curve analysis was performed for factors involved in insulin therapy, with the following cutoff values: fasting PG in the 75-g OGTT, 92 mg/dL; PG 30 min after MTT, 129 mg/dL; HOMA-IR, 1.51; DI, 3.9; HbA1c, 5.4%. Multivariate analysis revealed that the 30-min PG level after MTT and HOMA-IR predicted insulin therapy. Conclusion: PG levels at 30 min after MTT may be useful for identifying patients with GDM, who need insulin therapy.