Metformin is the most commonly prescibed drug for type 2 diabetes mellitus as it is inexpensive, safe, and efficient in ameliorating hyperglycemia and hyperinsulinemia. Numerous epidemiological studies indicate that diabetic population is not only at increased risk of cardiovascular complications, but also at substantially higher risk of many forms of malignancies. Meanwhile, epidemiological and clinical observation studies have shown that metformin use reduces risk of cancer in patients with type 2 diabetes mellitus and improves prognosis and survival rate of the cancer patients. Furthermore, metformin has been used for cancer therapy in clinical trials. Thus, metformin is emerging as a new cancer therapy or adjuvant anticancer drugs. This review summarizes recent progress in studies of metformin use and its molecular mechanism.
Antineoplastic Agents ; therapeutic use ; Diabetes Mellitus, Type 2 ; Humans ; Hyperglycemia ; Metformin ; therapeutic use ; Neoplasms ; drug therapy

PURPOSE: Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. MATERIALS AND METHODS: We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. RESULTS: The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). CONCLUSION: Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.
Chungcheongbuk-do ; Colorectal Neoplasms* ; Diagnosis ; Drug Therapy* ; Glucose ; Humans ; Hyperglycemia* ; Multivariate Analysis

Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.
Blood Platelets ; Diabetes Mellitus, Type 2/drug therapy* ; Humans ; Hyperglycemia/complications* ; Insulin Resistance ; Obesity/complications*

Humans ; Neutrophils ; Retrospective Studies ; Leukocyte Count ; Hyperglycemia/drug therapy* ; Insulins ; Insulin/therapeutic use*

OBJECTIVETo study the clinical features of neonatal diabetes mellitus (NDM).

METHODThirteen cases with NDM were seen in our department between Jul. 2004 and Sept. 2009. Their clinical features were reviewed retrospectively.

RESULTSThe average birth weight of the 13 cases was 2.30 kg. The median age at diagnosis was 2 months. The mean blood glucose at diagnosis was 22.2 mmol/L. Symptoms in 9 of 13 cases were exacerbated by infection and only 5 had typical symptoms of diabetes mellitus including polydipsia, polyuria, polyphagia and body weight loss. The common clinical findings included athrepsia, diuresis, and moderate dehydration. Ketoacidosis attacked 3 cases and 3 children had hypertriglyceridemia, meanwhile, 2 children had complications of blood clotting dysfunction and congenital cardiopathy, respectively. Autoantibody to insulin (IAA) was tested in 11 cases, all but one case was negative. Glycosylated hemoglobin was increased in 6 cases. Insulin treatment was started in all the 13 cases. The initial dose was 0.56-1.00 U/(kg × d), and the maximal dose was 1.35 U/(kg × d) depending on the variety of blood glucose. Blood glucose decreased significantly within 24 hours. Unfortunately, 1 case developed progressive blood glucose decline and recurrent hypoglycemia. Symptoms of the 3 cases who developed DKA were relieved 48 hours later, and their blood glucose was well under control. Among the 8 cases followed up, 4 had TNDM and 2 had PNDM. Unfortunately, 1 case died at the age of 3 months because insulin injection was stopped by the parents.

CONCLUSIONEarly diagnosis and prompt management may lead to favorable prognosis. Blood glucose monitoring is a valuable method to avoid misdiagnosis and NDM should be differentiated from stress hyperglycemia, iatrogenic, or other causes of hyperglycemia.

Blood Glucose ; analysis ; Diabetes Mellitus ; classification ; drug therapy ; Female ; Humans ; Hyperglycemia ; Infant ; Infant, Newborn ; Male ; Retrospective Studies

Small cell lung cancer(SCLC) is frequently associated with paraneoplastic syndromes, which occur in approximately 20% of patients at presentation. Clinical Cushing's syndrome secondary to ectopic ACTH production is uncommon, occurring in approximately 5% of all SCLC patients. However, biochemical evidence of hypercortisolism can be detected in up to 50% of patients. Patients with Cushing's syndrome from ectopic ACTH production show hypertension, weakness, hyperglycemia, and hypokalemic metabolic alkalosis, but differ from patients with classic Cushing's disease in that symptoms develop more rapidly. Ectopic ACTH production is associated with a poor response to chemotherapy, short survival, and a high risk of treatment-related complications. We report a case of Cushing's syndrome associated with ectopic corticotropin production in 59-year-old male patient with extensive stage of SCLC.
Adrenocorticotropic Hormone* ; Alkalosis ; Cushing Syndrome* ; Drug Therapy ; Humans ; Hyperglycemia ; Hypertension ; Lung Neoplasms* ; Lung* ; Male ; Middle Aged ; Paraneoplastic Syndromes

BACKGROUND: We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin. METHODS: A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24. RESULTS: The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups. CONCLUSION: In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.
Acarbose ; Diabetes Mellitus, Type 2 ; Drug Therapy, Combination ; Glucagon ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Incidence ; Insulin ; Korea ; Meals ; Metformin ; Sitagliptin Phosphate

Both diabetes mellitus and cancer are common diseases whose incidence is increasing globally. Epidemiologic evidence suggests that the prevalence of cancer is increasing in diabetic patients, and both hyperglycemia and hypoglycemia may lead to poor prognosis and complications in such patients undergoing cancer therapy. Nevertheless, managing glucose in patients with diabetes and cancer can pose a significant clinical challenge. As there are no evidence-based guidelines for treating diabetes in patients with cancer, an individualized approach is required. Diabetes self-management education is a critical element of care for cancer patients with diabetes. We discuss the management of diabetes in relation to cancer surgery, chemotherapy including glucocorticoids, and enteral and parenteral nutrition. We also discuss management of hyperglycemia in patients with advanced cancer approaching end of life care.
Diabetes Mellitus ; Drug Therapy ; Education ; Glucocorticoids ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia ; Incidence ; Parenteral Nutrition ; Prevalence ; Prognosis ; Self Care ; Terminal Care

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.
Mice ; Animals ; Hyperuricemia/drug therapy* ; Diet, High-Fat/adverse effects* ; Anthocyanins/chemistry* ; Ipomoea batatas/chemistry* ; Fructose/adverse effects* ; Hyperglycemia/drug therapy* ; Lipids

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.
Humans ; PPAR gamma/metabolism* ; Curcumin/therapeutic use* ; Phosphatidylinositol 3-Kinases ; Diabetes Mellitus/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Hyperglycemia/drug therapy* ; Glucose