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. 2009 Apr;58(4):773-95.
doi: 10.2337/db09-9028.

Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus

Ralph A Defronzo  1
Affiliations

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

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Figures

FIG. 1.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
FIG. 13.
The ominous octet. See text for a more detailed explanation.
FIG. 14.
FIG. 14.
Treatment of type 2 diabetes: a therapeutic approach based upon pathophysiology. See text for a more detailed explanation.
FIG. 15.
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.
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.
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.
FIG. 18.
ADA algorithm for the treatment of type 2 diabetes (49). See text for a more detailed explanation. SU, sulfonylurea.
FIG. 19.
FIG. 19.
Effect of insulin (Ins) and exenatide on A1C and body weight in type 2 diabetic subjects (–308).
FIG. 20.
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.
FIG. 21.
Pathophysiological-based algorithm: treatment of type 2 diabetes based upon pathophysiology. See text for a detailed discussion.
FIG. 22.
FIG. 22.
Comparison of the ADA and pathophysiological-based algorithms. See text for a detailed discussion.
See this image and copyright information in PMC

References

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