Fighting Diabetes Mellitus: Pharmacological and Non-pharmacological Approaches

Author(s): Xin Wang, Jinhong Kang, Qing Liu, Tao Tong*, Helong Quan*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 39 , 2020

Become EABM
Become Reviewer
Call for Editor


Background: The increasing worldwide prevalence of diabetes mellitus confers heavy public health issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost scientific challenges.

Objectives: This article aims to provide an overview of current pharmacological and non-pharmacological approaches available for the management of diabetes mellitus.

Methods: Research articles that focused on pharmacological and non-pharmacological interventions for diabetes were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes, glucagon-like peptide-1, glucose homeostasis, etc.

Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors- cyclic adenosine monophosphate, 5′-adenosine monophosphate-activated protein kinase, sodium-glucose cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods designed to mitigate diabetes are summarized and discussed.

Conclusion: Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2 inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent the most important strategies in diabetes management. These approved diabetes medications work via targeting the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is insufficient to achieve positive outcomes.

Keywords: Diabetes mellitus, cyclic adenosine monophosphate, G protein-coupled receptors, peroxisome proliferator activated-receptor gamma, sodium-glucose cotransporters 2, 5′-adenosine monophosphate-activated protein kinase, glucagon-like peptide-1 receptor, glucose homeostasis.

Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 2014; 383(9922): 1068-83.
[] [PMID: 24315620]
Sbroma Tomaro E, Pippi R, Reginato E, et al. Intensive lifestyle intervention is particularly advantageous in poorly controlled type 2 diabetes. Nutr Metab Cardiovasc Dis 2017; 27(8): 688-94.
[] [PMID: 28735815]
Saeedi P, Petersohn I, Salpea P, et al. 2019; pp. 157-107843. IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract
[] [PMID: 31518657]
Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414(6865): 782-7.
[] [PMID: 11742409]
Acharjee S, Ghosh B, Al-Dhubiab BE, Nair AB. Understanding type 1 diabetes: etiology and models. Can J Diabetes 2013; 37(4): 269-76.
[] [PMID: 24070892]
Papatheodorou K, Papanas N, Banach M, Papazoglou D, Edmonds M. Complications of Diabetes 2016. J Diabetes Res 2016; •••20166989453
[] [PMID: 27822482]
Xu X, Wang G, Zhou T, Chen L, Chen J, Shen X. Novel approaches to drug discovery for the treatment of type 2 diabetes. Expert Opin Drug Discov 2014; 9(9): 1047-58.
[] [PMID: 25054271]
Dowarah J, Singh VP. Anti-diabetic drugs recent approaches and advancements. Bioorg Med Chem 2020; 28(5)115263
[] [PMID: 32008883]
Muoio DM, Newgard CB. Mechanisms of disease:Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9(3): 193-205.
[] [PMID: 18200017]
Thulé PM. Mechanisms of current therapies for diabetes mellitus type 2. Adv Physiol Educ 2012; 36(4): 275-83.
[] [PMID: 23209008]
Tong T, Yu R, Park T. α-Cedrene protects rodents from high-fat diet-induced adiposity via adenylyl cyclase 3. Int J Obes 2019; 43(1): 202-16.
[] [PMID: 30568259]
Xu L, Li Y, Dai Y, Peng J. Natural products for the treatment of type 2 diabetes mellitus: Pharmacology and mechanisms. Pharmacol Res 2018; 130: 451-65.
[] [PMID: 29395440]
Fruchter O. Prevention of type 2 diabetes mellitus by changes in lifestyle. N Engl J Med 2001; 345(9): 696.
[] [PMID: 11547728]
Guo S. Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. J Endocrinol 2014; 220(2): T1-T23.
[] [PMID: 24281010]
Sato M, Dehvari N, Oberg AI, et al. Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle. Diabetes 2014; 63(12): 4115-29.
[] [PMID: 25008179]
Lin HV, Accili D. Hormonal regulation of hepatic glucose production in health and disease. Cell Metab 2011; 14(1): 9-19.
[] [PMID: 21723500]
Patel BM, Goyal RK. Liver and insulin resistance: New wine in old bottle!!! Eur J Pharmacol 2019; •••862172657
[] [PMID: 31499040]
Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell 2012; 148(5): 852-71.
[] [PMID: 22385956]
Sebastiani G, Ceccarelli E, Castagna MG, Dotta F. G-protein-coupled receptors (GPCRs) in the treatment of diabetes: Current view and future perspectives. Best Pract Res Clin Endocrinol Metab 2018; 32(2): 201-13.
[] [PMID: 29678286]
Jones DT, Reed RR. Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. Science 1989; 244(4906): 790-5.
[] [PMID: 2499043]
Blad CC, Tang C, Offermanns S. G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat Rev Drug Discov 2012; 11(8): 603-19.
[] [PMID: 22790105]
Ulloa-Aguirre A, Stanislaus D, Janovick JA, Conn PM. Structure-activity relationships of G protein-coupled receptors. Arch Med Res 1999; 30(6): 420-35.
[] [PMID: 10714355]
Kaihara KA, Dickson LM, Jacobson DA, et al. β-Cell-specific protein kinase A activation enhances the efficiency of glucose control by increasing acute-phase insulin secretion. Diabetes 2013; 62(5): 1527-36.
[] [PMID: 23349500]
Li E, Shan H, Chen L, et al. OLFR734 mediates glucose metabolism as a receptor of asprosin. Cell Metab 2019; 30: 319-28.
Gromada J, Bokvist K, Ding WG, et al. Adrenaline stimulates glucagon secretion in pancreatic A-cells by increasing the Ca2+ current and the number of granules close to the L-type Ca2+ channels. J Gen Physiol 1997; 110(3): 217-28.
[] [PMID: 9276750]
Klein J, Fasshauer M, Ito M, Lowell BB, Benito M, Kahn CR. beta(3)-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes. J Biol Chem 1999; 274(49): 34795-802.
[] [PMID: 10574950]
Chen M, Gavrilova O, Liu J, et al. Alternative Gnas gene products have opposite effects on glucose and lipid metabolism. Proc Natl Acad Sci USA 2005; 102(20): 7386-91.
[] [PMID: 15883378]
Richards P, Parker HE, Adriaenssens AE, et al. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes 2014; 63(4): 1224-33.
[] [PMID: 24296712]
MacDonald PE, El-Kholy W, Riedel MJ, Salapatek AM, Light PE, Wheeler MB. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes 2002; 51(Suppl. 3): S434-42.
[] [PMID: 12475787]
De Marinis YZ, Salehi A, Ward CE, et al. GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab 2010; 11(6): 543-53.
[] [PMID: 20519125]
Li WH. Functional analysis of islet cells in vitro, in situ, and in vivo. Semin Cell Dev Biol 2020; 103: 14-9.
[] [PMID: 32081627]
Ahrén B. Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov 2009; 8(5): 369-85.
[] [PMID: 19365392]
Kaihara KA, Dickson LM, Ellenbroek JH, Orr CM, Layden BT, Wicksteed B. PKA Enhances the Acute Insulin Response Leading to the Restoration of Glucose Control. Diabetes 2015; 64(5): 1688-97.
[] [PMID: 25475437]
Xie T, Chen M, Zhang QH, Ma Z, Weinstein LS. Beta cell-specific deficiency of the stimulatory G protein alpha-subunit Gsalpha leads to reduced beta cell mass and insulin-deficient diabetes. Proc Natl Acad Sci USA 2007; 104(49): 19601-6.
[] [PMID: 18029451]
Ding WG, Renström E, Rorsman P, Buschard K, Gromada J. Glucagon-like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism. Diabetes 1997; 46(5): 792-800.
[] [PMID: 9133546]
Yang H, Yang L. Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy. J Mol Endocrinol 2016; 57(2): R93-R108.
[] [PMID: 27194812]
Gonzalez GA, Montminy MR. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989; 59(4): 675-80.
[] [PMID: 2573431]
Tong T, Ryu SE, Min Y, et al. Olfactory receptor 10J5 responding to α-cedrene regulates hepatic steatosis via the cAMP-PKA pathway. Sci Rep 2017; 7(1): 9471.
[] [PMID: 28842679]
Tong T, Park J, Moon C, Park T. Regulation of adipogenesis and thermogenesis through mouse olfactory receptor 23 stimulated by alpha-cedrene in 3T3-L1 cells. Nutrients 2018; 10(11): 1781.
[] [PMID: 30453511]
DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992; 15(3): 318-68.
[] [PMID: 1532777]
Smith U. Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance--is insulin resistance initiated in the adipose tissue? Int J Obes Relat Metab Disord 2002; 26(7): 897-904.
[] [PMID: 12080441]
Keung W, Ussher JR, Jaswal JS, et al. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice. Diabetes 2013; 62(3): 711-20.
[] [PMID: 23139350]
Nevzorova J, Bengtsson T, Evans BA, Summers RJ. Characterization of the beta-adrenoceptor subtype involved in mediation of glucose transport in L6 cells. Br J Pharmacol 2002; 137(1): 9-18.
[] [PMID: 12183326]
Nevzorova J, Evans BA, Bengtsson T, Summers RJ. Multiple signalling pathways involved in beta2-adrenoceptor-mediated glucose uptake in rat skeletal muscle cells. Br J Pharmacol 2006; 147(4): 446-54.
[] [PMID: 16415914]
Mukaida S, Evans BA, Bengtsson T, Hutchinson DS, Sato M. Adrenoceptors promote glucose uptake into adipocytes and muscle by an insulin-independent signaling pathway involving mechanistic target of rapamycin complex 2. Pharmacol Res 2017; 116: 87-92.
[] [PMID: 28025104]
Allen JA, Yu JZ, Donati RJ, Rasenick MM. Beta-adrenergic receptor stimulation promotes G alpha s internalization through lipid rafts: a study in living cells. Mol Pharmacol 2005; 67(5): 1493-504.
[] [PMID: 15703379]
Lee NJ, Nguyen AD, Enriquez RF, et al. NPY signalling in early osteoblasts controls glucose homeostasis. Mol Metab 2015; 4(3): 164-74.
[] [PMID: 25737952]
Janani C, Ranjitha Kumari BD. PPAR gamma gene-a review. Diabetes Metab Syndr 2015; 9(1): 46-50.
[] [PMID: 25450819]
Rosen ED, Spiegelman BM. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 2001; 276(41): 37731-4.
[] [PMID: 11459852]
He W, Barak Y, Hevener A, et al. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci USA 2003; 100(26): 15712-7.
[] [PMID: 14660788]
Kintscher U, Law RE. PPARgamma-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab 2005; 288(2): E287-91.
[] [PMID: 15637349]
Wang S, Dougherty EJ, Danner RL. PPARγ signaling and emerging opportunities for improved therapeutics. Pharmacol Res 2016; 111: 76-85.
[] [PMID: 27268145]
Day EA, Ford RJ, Steinberg GR. AMPK as a therapeutic target for treating metabolic diseases. Trends Endocrinol Metab 2017; 28(8): 545-60.
[] [PMID: 28647324]
Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes 2014; 7: 241-53.
[PMID: 25018645]
O’Neill HM, Maarbjerg SJ, Crane JD, et al. AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci USA 2011; 108(38): 16092-7.
[] [PMID: 21896769]
Rourke JL, Hu Q, Screaton RA. AMPK and friends: central regulators of beta cell biology. Trends Endocrinol Metab 2018; 29(2): 111-22.
[] [PMID: 29289437]
Ivanova MI, Sievers SA, Sawaya MR, Wall JS, Eisenberg D. Molecular basis for insulin fibril assembly. Proc Natl Acad Sci USA 2009; 106(45): 18990-5.
[] [PMID: 19864624]
Bailey CJ. Metformin: historical overview. Diabetologia 2017; 60(9): 1566-76.
[] [PMID: 28776081]
Tu YY, Ni MY, Zhong YR, et al. Yao Xue Xue Bao 1981; 16(5): 366-70. Tu YY, Ni MY, Zhong YR, et al. [Studies on the constituents of Artemisia annua L. (author’s transl)]. Yao Xue Xue Bao 1981; 16(5): 366-70. [Studies on the constituents of Artemisia annua L. (author's transl)].
[PMID: 7246183]
Zhou T, Xu X, Du M, Zhao T, Wang J. A preclinical overview of metformin for the treatment of type 2 diabetes. Biomed Pharmacother 2018; 106: 1227-35.
[] [PMID: 30119191]
Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108(8): 1167-74.
[] [PMID: 11602624]
Duca FA, Côté CD, Rasmussen BA, et al. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. Nat Med 2015; 21(5): 506-11.
[] [PMID: 25849133]
Miller RA, Chu Q, Xie J, Foretz M, Viollet B, Birnbaum MJ. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 2013; 494(7436): 256-60.
[] [PMID: 23292513]
Caesar R. Pharmacologic and nonpharmacologic therapies for the gut microbiota in type 2 diabetes. Can J Diabetes 2019; 43(3): 224-31.
[] [PMID: 30929665]
Y-J.H. Thiazolidinediones . N Engl J Med 2004; 351: 1106-18.
[] [PMID: 15356308]
Bansal G, Thanikachalam PV, Maurya RK, Chawla P, Ramamurthy S. An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes. J Adv Res 2020; 23: 163-205.
[] [PMID: 32154036]
[67] European Medicines Agency. Questions and answers on the review of pioglitazone-containing medicines (Actos, Glustin, Competact, Glubrava and Tandemact). Available at:
Lee JH, Noh CK, Yim CS, et al. Kinetics of the absorption, distribution, metabolism, and excretion of lobeglitazone, a novel activator of peroxisome proliferator-activated receptor gamma in rats. J Pharm Sci 2015; 104(9): 3049-59.
[] [PMID: 25648999]
Nanjan MJ, Mohammed M, Prashantha Kumar BR, Chandrasekar MJN. Thiazolidinediones as antidiabetic agents: A critical review. Bioorg Chem 2018; 77: 548-67.
[] [PMID: 29475164]
Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86(8): 3717-23.
[] [PMID: 11502801]
D’Alessio DA, Vahl TP. Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes. Am J Physiol Endocrinol Metab 2004; 286(6): E882-90.
[] [PMID: 15140755]
Underwood CR, Garibay P, Knudsen LB, et al. Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor. J Biol Chem 2010; 285(1): 723-30.
[] [PMID: 19861722]
Drucker DJ, Sherman SI, Gorelick FS, Bergenstal RM, Sherwin RS, Buse JB. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care 2010; 33(2): 428-33.
[] [PMID: 20103558]
Svegliati-Baroni G, Saccomanno S, Rychlicki C, et al. Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver Int 2011; 31(9): 1285-97.
[] [PMID: 21745271]
American Diabetes Association 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care 2018; 41(Suppl. 1): S73-85.
[] [PMID: 29222379]
Khunti K, Chatterjee S, Gerstein HC, Zoungas S, Davies MJ. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol 2018; 6(10): 821-32.
[] [PMID: 29501322]
Whitlock RH, Hougen I, Komenda P, Rigatto C, Clemens KK, Tangri N. A safety comparison of metformin vs sulfonylurea initiation in patients with type 2 diabetes and chronic kidney disease: a retrospective cohort study. Mayo Clin Proc 2020; 95(1): 90-100.
[] [PMID: 31902433]
Hediger MA, Rhoads DB. Molecular physiology of sodium-glucose cotransporters. Physiol Rev 1994; 74(4): 993-1026.
[] [PMID: 7938229]
Storgaard H, Gluud LL, Bennett C, et al. Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One 2016; 11(11)e0166125
[] [PMID: 27835680]
Van Beers EH, Büller HA, Grand RJ, Einerhand AW, Dekker J. Intestinal brush border glycohydrolases: structure, function, and development. Crit Rev Biochem Mol Biol 1995; 30(3): 197-262.
[] [PMID: 7555019]
Langer O. Pharmacological treatment of gestational diabetes mellitus: point/counterpoint. Am J Obstet Gynecol 2018; 218(5): 490-9.
[] [PMID: 29499921]
Ahrén B. Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin. Vasc Health Risk Manag 2008; 4(2): 383-94.
[] [PMID: 18561513]
Nauck M, Frid A, Hermansen K, et al. LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009; 32(1): 84-90.
[] [PMID: 18931095]
Díaz-Trastoy O, Villar-Taibo R, Sifontes-Dubón M, et al. GLP1 receptor agonist and SGLT2 inhibitor combination: An effective approach in real-life clinical practice. Clin Ther 2020; 42(2): e1-e12.
[] [PMID: 32005534]
Rosenstock J, Hansen L, Zee P, et al. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care 2015; 38(3): 376-83.
[] [PMID: 25352655]
Ramsay RR, Popovic-Nikolic MR, Nikolic K, Uliassi E, Bolognesi ML. A perspective on multi-target drug discovery and design for complex diseases. Clin Transl Med 2018; 7(1): 3.
[] [PMID: 29340951]
Li G, Meng B, Yuan B, et al. The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119. Eur J Med Chem 2020; •••188112017
[] [PMID: 31926470]
Li G, Huan Y, Yuan B, et al. Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents. Eur J Med Chem 2016; 124: 103-16.
[] [PMID: 27560285]
Hahr AJ, Molitch ME. Management of diabetes mellitus in patients with chronic kidney disease. Clin Diabetes Endocrinol 2015; 1: 2.
[] [PMID: 28702221]
Zheng W, Thorne N, McKew JC. Phenotypic screens as a renewed approach for drug discovery. Drug Discov Today 2013; 18(21-22): 1067-73.
[] [PMID: 23850704]
Sharma AK, Bharti S, Ojha S, et al. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br J Nutr 2011; 106(11): 1713-23.
[] [PMID: 21736771]
Gu JJ, Gao FY, Zhao TY. A preliminary investigation of the mechanisms underlying the effect of berberine in preventing high-fat diet-induced insulin resistance in rats. J Physiol Pharmacol 2012; 63(5): 505-13.
[PMID: 23211304]
Cao H, Ou J, Chen L, et al. Dietary polyphenols and type 2 diabetes: Human Study and Clinical Trial. Crit Rev Food Sci Nutr 2019; 59(20): 3371-9.
[] [PMID: 29993262]
Elekofehinti OO. Saponins: Anti-diabetic principles from medicinal plants - A review. Pathophysiology 2015; 22(2): 95-103.
[] [PMID: 25753168]
He JH, Chen LX, Li H. Progress in the discovery of naturally occurring anti-diabetic drugs and in the identification of their molecular targets. Fitoterapia 2019; 134: 270-89.
[] [PMID: 30840917]
Raveendran AV, Chacko EC, Pappachan JM. Non-pharmacological Treatment Options in the Management of Diabetes Mellitus. Eur Endocrinol 2018; 14(2): 31-9.
[] [PMID: 30349592]
Gregg EW, Chen H, Wagenknecht LE, et al. Look AHEAD Research GroupAssociation of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA 2012; 308(23): 2489-96.
[] [PMID: 23288372]
Franz MJ, MacLeod J. Success of nutrition-therapy interventions in persons with type 2 diabetes: challenges and future directions. Diabetes Metab Syndr Obes 2018; 11: 265-70.
[] [PMID: 29928137]
Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20(4): 537-44.
[] [PMID: 9096977]
Andreas Storz M, Iraci F. Short-term dietary oatmeal interventions in adults with type 2 diabetes: a forgotten tool. Can J Diabetes 2019.
[] [PMID: 31866240]
Cartee GD, Holloszy JO. Exercise increases susceptibility of muscle glucose transport to activation by various stimuli. Am J Physiol 1990; 258(2 Pt 1): E390-3.
[PMID: 2305881]
García-Hermoso A, Saavedra JM, Escalante Y, Sánchez-López M, Martínez-Vizcaíno V. Endocrinology and Adolescence: aerobic exercise reduces insulin resistance markers in obese youth: a meta-analysis of randomized controlled trials. Eur J Endocrinol 2014; 171(4): R163-71.
[] [PMID: 24920290]
Dos Santos JM, Moreli ML, Tewari S, Benite-Ribeiro SA. The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective. Metabolism 2015; 64(12): 1619-28.
[] [PMID: 26481513]
Allin KH, Tremaroli V, Caesar R, et al. IMI-DIRECT consortium Aberrant intestinal microbiota in individuals with prediabetes. Diabetologia 2018; 61(4): 810-20.
[] [PMID: 29379988]
Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine 2020; 5110: 2590.
[] [PMID: 31901868]
Kootte RS, Levin E, Salojarvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab 2017; 26: 611-9.
Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143: 913-6.
Quintal A, Messier V, Rabasa-Lhoret R, Racine E. A critical review and analysis of ethical issues associated with the artificial pancreas. Diabetes Metab 2019; 45(1): 1-10.
[] [PMID: 29753624]
Rege NK, Phillips NFB, Weiss MA. Development of glucose-responsive ‘smart’ insulin systems. Curr Opin Endocrinol Diabetes Obes 2017; 24(4): 267-78.
[] [PMID: 28509691]
Aguayo-Mazzucato C, Bonner-Weir S. Pancreatic beta cell regeneration as a possible therapy for diabetes. Cell Metab 2018; 27(1): 57-67.
[] [PMID: 28889951]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 10 November, 2020
Page: [4992 - 5001]
Pages: 10
DOI: 10.2174/1381612826666200728144200
Price: $65

Article Metrics

PDF: 27