Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus - PubMed (original) (raw)
Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus
Ralph A Defronzo. Diabetes. 2009 Apr.
No abstract available
Figures
FIG. 1.
Pathogenesis of type 2 diabetes: the triumvirate. Insulin resistance in muscle and liver and impaired insulin secretion represent the core defects in type 2 diabetes (1). See text for a more detailed explanation.
FIG. 2.
Natural history of type 2 diabetes. The plasma insulin response (○) depicts the classic Starling's curve of the pancreas (1). See text for a more detailed explanation. ●, insulin-mediated glucose uptake (top panel).
FIG. 3.
Insulin secretion/insulin resistance (disposition) index (ΔI/ΔG ÷ IR) in individuals with NGT, IGT, and type 2 diabetes (T2DM) as a function of the 2-h plasma glucose (PG) concentration in lean and obese subjects (–42).
FIG. 4.
Natural log of the 2-h plasma glucose (PG) concentration versus natural log of the insulin secretion/insulin resistance index (measure of β-cell function) (–42). T2DM, type 2 diabetes.
FIG. 5.
Effect of physiological elevation (48 h) in the plasma FFA concentration (brought about by lipid infusion) on plasma C-peptide concentration (left) and insulin secretory response (deconvolution of the palsma C-peptide curve) (right) in offspring of two type 2 diabetic parents (24).
FIG. 6.
First-phase (0–10 min) and second-phase (10–120 min) plasma insulin response during hyperglycemic clamp in partially pancreatectomized diabetic (DIAB) and control (CON) rats (77). PHLOR, phlorizin.
FIG. 7.
Basal HGP (left) in control and type 2 diabetic (T2DM) subjects. The relationship between basal HGP and fasting plasma glucose (FPG) concentration is shown on the right (1,25).
FIG. 8.
Insulin-stimulated total body glucose uptake (left) and insulin-stimulated leg glucose uptake (right) in control (CON) and type 2 diabetic (T2DM) subjects (28,29).
FIG. 9.
Relationship between impaired insulin signal transduction and accelerated atherogenesis in insulin-resistant subjects, i.e., type 2 diabetes and obesity (126,143).
FIG. 10.
Hepatic glucose uptake in nondiabetic and diabetic (DIAB) subjects as a function of plasma glucose and insulin concentrations and route of glucose administration (–174).
FIG. 11.
Effect of lipid infusion to cause a physiological-pharmacological elevation in plasma FFA concentration on insulin signal transduction in healthy nondiabetic subjects (201). PY, phosphorylation.
FIG. 12.
SGLT 2 transporter mRNA (left) and protein (middle) and glucose transport (α-methyl-
d
-glucopyranoside) (right) are increased in cultured renal proximal tubular epithelial cells of individuals with type 2 diabetes (T2DM) versus nondiabetic subjects (CON) (232).
FIG. 13.
The ominous octet. See text for a more detailed explanation.
FIG. 14.
Treatment of type 2 diabetes: a therapeutic approach based upon pathophysiology. See text for a more detailed explanation.
FIG. 15.
The effect of sulfonylurea (glibenclamide = glyburide) and metformin therapy on the plasma A1C concentration in newly diagnosed type 2 diabetic subjects. Conventionally treated diabetic subjects received diet plus exercise therapy (36,279).
FIG. 16.
Summary of studies examining the effect of sulfonylurea (SU) treatment versus placebo or versus active-comparator on A1C in type 2 diabetic subjects (,,,,–,–285). See text for a more detailed discussion. GLY, glyburide.
FIG. 17.
Summary of studies examining the effect of TZDs versus placebo or versus active-comparator on A1C in type 2 diabetic subjects (,,,–273). See text for a more detailed discussion. PIO, pioglitazone; ROSI, rosiglitazone.
FIG. 18.
ADA algorithm for the treatment of type 2 diabetes (49). See text for a more detailed explanation. SU, sulfonylurea.
FIG. 19.
Effect of insulin (Ins) and exenatide on A1C and body weight in type 2 diabetic subjects (–308).
FIG. 20.
ADA consensus statement algorithm on the treatment of type 2 diabetes. As indicated, this does not represent the official statement of ADA (49). See text for a detailed discussion (309). Exen, exenatide; PIO, pioglitazone; SU, sulfonylurea.
FIG. 21.
Pathophysiological-based algorithm: treatment of type 2 diabetes based upon pathophysiology. See text for a detailed discussion.
FIG. 22.
Comparison of the ADA and pathophysiological-based algorithms. See text for a detailed discussion.
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