the blood sugar diet

πŸ”₯+ the blood sugar diet 06 Jul 2020 Written in partnership with TCOYD - Taking Control of Your Diabetes. Medically reviewed in October 2018. Even ...

the blood sugar diet β€œIt might also lead to new treatments, if we can find ways to reactivate dormant insulin-producing cells in the older age group. This would be a ...

diabetes online community pdf
the blood sugar diet exhaustion (πŸ”΄ usually appears after age 40) | the blood sugar diet patchhow to the blood sugar diet for Clin Med Res. 2003 Jul; 1(3): 189–200.
the blood sugar diet natural (⭐️ fasting blood sugar goal) | the blood sugar diet listhow to the blood sugar diet for doi: 10.3121/cmr.1.3.189
PMCID: PMC1069045
PMID: 15931309

the blood sugar diet in skinny people (β˜‘ patch) | the blood sugar diet natural remedieshow to the blood sugar diet for Michael T. Sheehan

Department of Endocrinology, Marshfield Clinic-Wausau Center, Wausau, Wisconsin

Find articles by Michael T. Sheehan
Michael T. Sheehan, Department of Endocrinology, Marshfield Clinic-Wausau Center, Wausau, Wisconsin;
REPRINT REQUESTS: Michael T. Sheehan, MD Department of Endocrinology Marshfield Clinic-Wausau Center 2727 Plaza Drive Wausau, WI 54401 Telephone: 715-847-3550 Fax: 715-847-3039 Email: [email protected]
DISCLOSURE: Dr. Sheehan serves on the Speaker Bureaus for the following pharmaceutical companies: Takeda, GlaxoSmithKline, Lilly, Aventis and Pfizer.
Received 2003 Mar 31; Accepted 2003 Jun 11.
Copyright ©2003 Clinical Medicine & Research
This article has been cited by other articles in PMC.

Abstract

The incidence of type 2 diabetes mellitus (DM) in the United States continues to grow rapidly, paralleling the overweight and obesity epidemic. For many years the only therapeutic options for type 2 DM were sulfonylureas and insulin. However, over the last 9 years there has been an explosion of new and exciting agents approved for the treatment of type 2 DM. Some of the treatments target insulin deficiency and others insulin resistance, the hallmarks of the disease. Other drugs delay the intestinal absorption of carbohydrate. Recently several combination agents have been released. With these new drugs has come an overwhelming mountain of information, making it difficult for the busy clinician to know how best to manage the ever-increasing portion of patients with type 2 DM.

the blood sugar diet urine test (πŸ”₯ treat) | the blood sugar diet wikihow to the blood sugar diet for New questions have arisen: Which agent to start as first line? How much of this drug to use before adding something else? How long for this drug to reach full effect? Which agent to add second? Should a patient uncontrolled on dual therapy begin insulin or start a third oral agent? If insulin therapy is started, what should become of the patient''s weight gain on therapy? These are not easy questions and no review can fully detail all the therapeutic combinations possible. Instead, the practical approach of reviewing the agents in terms of their mechanism of action and critically comparing their dosing, effect and cost, is undertaken herein. Also addressed is the possible niche some newer classes of agents and combination drugs may or may not hold in the management of type 2 DM. The decision of using insulin versus a third oral agent will be looked at from the standpoint of where the patient is on dual therapy in relation to the hemoglobin A1c goal. In this way it is hoped that some clarity will be brought to the dizzying array of information that both the physician and patient have to deal with in regard to the management of this prevalent and serious disease.

Keywords: Type 2 DM, Insulin secretagogues, Insulin sensitizers, Diabetes therapy, Glucose absorption inhibitors

INTRODUCTION

Vast amounts of literature have been written about the current and growing epidemic of diabetes mellitus (DM) and its associated complications. The cost of diabetes to the United States healthcare system is staggering, amounting to $100 billion in direct and indirect expenditures annually.1 Currently 15 million Americans have diabetes, one third of whom have yet to be diagnosed. Ninety percent of these cases represent type 2 DM. The incidence of type 2 DM and its precursor (impaired glucose tolerance) continues to rise, paralleling that of overweight and obesity.2 Frighteningly, this is occurring in children and adolescents, as well as adults.3 Over the last 9 years a growing number of oral medications and newer insulin analogs have become available for use in type 2 DM. The optimal use of these agents has become more difficult with the increased complexity a greater number of choices bring. This task is made more challenging with the pharmaceutical industry spending large sums of money annually in direct marketing toward physicians and patients.4 For better or worse, prescribing patterns are affected by this marketing, or obviously such amounts of money would not be so spent.5

It should be stressed that despite the vast literature available, many patients and physicians alike still view type 2 DM as a “less severe” illness than type 1 DM. On the contrary, because of the much greater prevalence of type 2 DM, the great majority of microvascular complications occurs in these patients. The increased risk of cardiovascular disease (CVD) in type 2 DM has led to more stringent goals for the management of cholesterol and blood pressure, in addition to the use of aspirin.6 Therefore, close attention should be paid to the overall cardiovascular health of patients with type 2 DM, not just their hemoglobin A1c (HbA1c).

the blood sugar diet webmd (πŸ‘ quick facts) | the blood sugar diet questionnairehow to the blood sugar diet for The optimal management of type 2 DM cannot be discussed by simply outlining what agents are available along with their doses, effectiveness and side effects. More difficult management issues need to be explored as well. Also, as CVD is so prevalent in patients with type 2 DM the potential for non-glycemic benefits of some of the newer agents deserves mention. This review will focus not only on the oral agents per se, but also on their proper use over time and in combination. The potential benefit of non-glycemic effects of some agents will be mentioned briefly. The use of insulin in combination with oral agents will also be described. It is hoped that through a better understanding of these agents providers of care for patients with type 2 DM will be aided in the most difficult task of preventing the complications of the disease.

ORAL AGENTS AVAILABLE FOR THE TREATMENT OF TYPE 2 DM

Prior to 1994 selecting an oral agent for the treatment of type 2 DM was as simple as choosing which sulfonylurea (SU) to use. Since then, a variety of newer agents with unique mechanisms of action and even some combination agents have been released for use as monotherapy or in any number of combination regimens. This trend is likely to continue as even newer agents with completely different mechanisms of action are currently under investigation. Along with this explosion of therapeutic options has come uncertainty over how to use these agents effectively. When thought of the 1 last update 06 Jul 2020 simply, there are but three ways in which these agents work toward improving glycemic control: (1) increasing insulin secretion [insulin secretagogues], (2) increasing insulin action [insulin sensitizers], and (3) decreasing insulin need [inhibitors of glucose absorption].Prior to 1994 selecting an oral agent for the treatment of type 2 DM was as simple as choosing which sulfonylurea (SU) to use. Since then, a variety of newer agents with unique mechanisms of action and even some combination agents have been released for use as monotherapy or in any number of combination regimens. This trend is likely to continue as even newer agents with completely different mechanisms of action are currently under investigation. Along with this explosion of therapeutic options has come uncertainty over how to use these agents effectively. When thought of simply, there are but three ways in which these agents work toward improving glycemic control: (1) increasing insulin secretion [insulin secretagogues], (2) increasing insulin action [insulin sensitizers], and (3) decreasing insulin need [inhibitors of glucose absorption].

Increasing insulin secretion (secretagogues)

the blood sugar diet effects (πŸ”΄ naturally with diet) | the blood sugar diet biologyhow to the blood sugar diet for SULFONYLUREAS

These agents were first introduced for the management of type 2 DM in the mid-1950s. These were the only oral agents available in the United States until 1994. These drugs work by binding to a regulatory protein (commonly referred to as the SU receptor) on pancreatic β-cells, which in turn, results in closure of ATP-dependent potassium (KATP) channels leading to membrane depolarization and influx of calcium through voltage-dependent channels, which subsequently leads to insulin secretion.7

As the second generation SUs are currently the most widely used, this discussion will be limited to these agents. The dosing, and the cost and effect of the SUs on HbA1c are summarized in table 1. As is apparent, their relative potency is similar. The most common side effect of the SUs is hypoglycemia, the risk of which varies somewhat among the agents. It is generally accepted that glyburide has twice the risk of hypoglycemia compared to the other second generation SUs.8,9 This is due to increased duration of binding to the SU receptor, resulting in fasting hyperinsulinemia with glyburide. This degree of fasting hyperinsulinemia is generally not seen with the other SUs, which are more glucose-sensitive (and thus prandial) in their stimulation of insulin secretion.9 An additional factor in this regard is glyburide''s actual mechanism of action is not fully known, but its main effect is to decrease hepatic gluconeogenesis, thus improving fasting hyperglycemia.25 There is also a peripheral effect of improved insulin action in muscle tissue, which may be related to metformin''s opinion, is more strongly affected by physician-patient discussions that occur (or do not occur) in regard to combination therapy. An informed patient is more likely to comply with therapy than an uninformed or confused patient.

For a combination agent to be useful it should be comparable, if not less, in cost to its components and should involve fewer tablets daily (and/or decreased frequency of dosing). With this in mind, it is interesting to see that the various combination agents available do not fare well (table 2). Indeed, none offer fewer tablets daily than the components taken separately. In reference to cost, only Avandamet (GlaxoSmithKline, Research Triangle Park, NC) offers savings over its components separately (approximately $400 per year less). There is some unpublished, retrospective data suggesting that Glucovance lowers HbA1c to a greater degree than similar doses of metformin and glyburide separately. These results suggest a benefit of 0.13% to 0.6% with Glucovance. Until these results can be confirmed by a prospective, randomized trial, they should be interpreted with caution. Even if confirmed, the cost-effectiveness of this benefit (an additional $700 annually) is unclear.

Table 2

Cost comparison of combination agents versus component agents separately.

AgentMaximum effective dose (mg)Cost/year ($)aPills/dayComponent cost/year ($)aPills/day
Glucovance*2.5/500, 2 bid1,40047303
Avandamet*2/500, 2 bid2,17042,5504
Metaglip*5/500, 2 bid1,40047754

aAverage wholesale price for brand name and maximal allowable cost for generic preparations.

*Glucophage-XR, Glucovance for 1 last update 06 Jul 2020 and Metaglip (Bristol-Myers Squibb Company, Princeton, NJ); Avandamet (GlaxoSmithKline, Research Triangle Park, NC).*Glucophage-XR, Glucovance and Metaglip (Bristol-Myers Squibb Company, Princeton, NJ); Avandamet (GlaxoSmithKline, Research Triangle Park, NC).

Dual therapy options

As was shown in the UKPDS, most patients with type 2 DM will eventually require multiple oral agents to maintain optimal glycemic control. With the availability of newer agents that target not only the defect in insulin secretion, but also insulin action, a variety of combination strategies are now possible. A full discussion of these options is beyond the scope of this review, but several excellent summaries are available.56,57 In general, the combination of an insulin secretagogue and sensitizer is most often used and makes intuitive sense given the two major pathogenic mechanisms of type 2 DM (insulin resistance and insulin deficiency). Most often this involves the use of metformin and an SU, as this combination brings together high potency, low cost and a low potential for weight gain. Certainly, a TZD should be substituted for metformin in the case of contraindications to the latter. The use of non-SU secretagogues and/or AGIs brings increased cost, decreased potency, and more potential for side effects (with AGIs).

The potential utility of metformin plus a TZD as dual therapy is interesting. From the standpoint of annual cost, this combination ($2,500) is certainly more expensive than metformin plus SU (∼$800). Metformin plus TZD is also slightly less potent than metformin or TZD plus SU.56,57 However, despite both being insulin sensitizers, this combination still makes good pharmacologic sense, as each improves insulin resistance primarily in a different tissue. Also, there may be some potential for limiting weight gain with TZDs when used with metformin. Furthermore, with the data on preservation of β-cell function, a TZD may help preserve insulin secretory capacity and thus delay secondary failure of oral agent therapy.35,37,38 As well, this combination may allow for tighter glycemic control without the risk of severe hypoglycemia that using an SU might bring. Lastly, the beneficial effects on surrogate markers of CVD cannot help but make one think of the potential benefit of TZDs beyond lowering glucose. What might be the potential cost-benefit of early use of TZD therapy, if they are shown to prevent cardiovascular events and/or deaths?

Triple oral therapy or insulin initiation?

Perhaps one of the most difficult decisions in the management of type 2 DM has become whether to add a third oral agent or to start insulin therapy in an uncontrolled patient. This has only become an issue since the release of the TZDs several years ago. As mentioned previously, there may be several reasons why these agents should be used earlier in the course of treatment than is typically the case. TZDs have now been primarily used as third line agents and they will be discussed as such in this setting. There are three key issues that need considering when facing this decision.

First, how far from goal is the patient? This is important in terms of both whether to add a TZD or start insulin, also how intense an insulin program to start, if need be. The addition of a TZD as a third agent is beneficial in about 60% of patients.44 In those who respond the effect can be substantial with a mean HbA1c reduction of approximately 2.5% seen in a troglitazone trial.44 When taken as a whole (responders and non-responders alike), the mean reduction in HbA1c by adding troglitazone third line was only 1.4%.58 In the only published trial (in letter form) of the currently available TZDs, rosiglitazone added to glimepiride and metformin therapy,59 led to a 1.4% reduction in HbA1c. Patients whose HbA1c is above 9.5% on dual therapy are unlikely to get to goal by the addition of a TZD. A trial can be given to these patients (especially those particularly averse to insulin therapy), but follow-up for consideration of other options should be scheduled after 3 months at maximal dose. The TZD should be discontinued if the patient does not respond. If the decision to start insulin is made it should be stressed that adding bedtime insulin to daytime oral agent therapy will only lower HbA1c by 2% to 2.5%.60 Therefore, if the HbA1c is above 9.5% on dual therapy, the patient is likely to need a more intensive insulin program. Also, there is no evidence that bedtime glargine insulin results in better glycemic control than bedtime neutral protamine Hagedorn (NPH) insulin, although there is certainly less hypoglycemia with the former.61 Use of glargine insulin increases costs by 65% versus NPH insulin. As is noted in table 3, triple oral agent therapy costs over twice as much as SU and metformin plus bedtime NPH insulin for a similar reduction in HbA1c.

Table 3

Cost comparison of triple oral the 1 last update 06 Jul 2020 therapy (adding thiazolidinediones) versus institution of various insulin programs in patients uncontrolled on sulfonylureas (SU) and metformin combination therapy.Cost comparison of triple oral therapy (adding thiazolidinediones) versus institution of various insulin programs in patients uncontrolled on sulfonylureas (SU) and metformin combination therapy.

TherapyaCost/year ($)bHbA1c reduction (%)Comments
SU maximal dosec +
metformin 1000 bid900N/ABaseline
SU maximal dose +
metformin 1000 bid +1.4 overall58,59
TZD maximal dosed2,9002.5 for responders44∼60% response rate44
SU maximal dose +
metformin 1000 bid +
Bedtime NPHf1,2001.5–2.020 units/day60
NPH and regular bid or1,400120 units/daye (70% NPH; 30% short-acting insulin)
NPH and Humalog/NovoLog bidg1,900Based on dosage
metformin 1000 bid +
NPH and regular bid or1,65082 units/day62,63 (70% NPH: 30% short-acting insulin)
NPH and Humalog/NovoLog bid1,950Based on dosage
SU maximal dose +
metformin 1000 bid +
NPH and regular bid or1,60046 units/day62,63 (70% NPH; 30% short-acting insulin)
NPH and Humalog/NovoLog bid1,800Based on dosage

a Insulin doses for oral agents plus insulin regimens represent “insulin-sparing” effects of oral agents as described in references noted.

b Average wholesale price for brand name and maximal allowable cost for generic (oral agents ± insulin vials) (syringes included).

the blood sugar diet epidemiology (πŸ‘ zero to finals) | the blood sugar diet bornhow to the blood sugar diet for c SU (sulfonylurea), Glipizide-GITS 10 mg qd or glimepiride 4 mg qd.

d TZD (thiazolidinediones), pioglitazone 45 qd or rosiglitazone 4 bid.

e Insulin dosage assumes a 100 kg patient requiring 1.2 units/kg/day.

f NPH, neutral protamine Hagedorn.

g Humalog (Eli Lilly and Company, Indianapolis, IN ); NovoLog (Novo Nordisk Pharmaceuticals, Inc., Princeton, NJ).

Second, if insulin is started, which oral agent(s) should be stopped? This will depend on the type of insulin program contemplated. If bedtime insulin is chosen, then daytime oral agents should be continued. However, if a more intensive insulin program is started, then three options should be considered: (1) continue both the SU and metformin, (2) stop the SU and continue metformin, (3) discontinue both oral agents. Provided appropriate adjustments in insulin are made, each of these three options will likely result in a similar improvement in HbA1c. The cost is surprisingly similar as well, owing to the differences in total insulin dose that will be needed to achieve control (i.e., continuing oral agents will result in less insulin being needed) (table 3).62,63 Continuation of metformin makes intuitive sense, as its mechanism compliments that of insulin and tends to lessen any weight gain that might occur. On the contrary, an SU works in relatively the same manner as insulin and thus is often discontinued. It should be remembered, that the SU is often still having some, albeit an inadequate, effect on glucose control. If discontinued, the SU effect will dissipate quickly, allowing glucose levels to sometimes rise dramatically. The physician should relay this possibility to the patient so as to not mislead them into believing that the insulin is not working and they were “better off on pills.” This may be particularly important in patients who have been very resistant to insulin and in those who are less likely to be compliant with scheduled follow-up. Continuation of both the SU and metformin may be best in these patients. Interestingly, the incremental cost of using fast-acting insulin analogs versus regular insulin becomes less as one or more oral agents are continued with insulin initiation due to an “insulin-sparing” effect of oral agents (table 3). As β-cell failure progresses, an increase in exogenous insulin will be required, thus rendering the continued use of the SU less cost-neutral.

the blood sugar diet vaccine (πŸ‘ treatment and prevention) | the blood sugar diet breakfasthow to the blood sugar diet for Lastly, what type of insulin program should be started? While a complete discussion of insulin options beyond bedtime dosing only is impossible here, one of the most common strategies is to employ a twice-daily regimen of an intermediately-acting insulin mixed with a short-acting insulin (figure 3). Whether self-mixing of insulin or premixed formulations are used is a matter of preference, but the author prefers the former for its greater flexibility, which allows tighter control with less hypoglycemia. However, self-mixing of insulin may result in less accuracy. The choice of regular insulin versus an insulin analog can be debated. Most often this debate centers on cost-benefit issues as each vial of an insulin analog is priced approximately $34 more than regular insulin. As previously mentioned, this incremental cost becomes less of an issue as oral agents are used with insulin. There is good evidence that both insulin analogs result in improvements in HbA1c (Humalog, 0.3% to 0.4% [Eli Lilly and Company, Indianapolis, IN] and NovoLog, 0.12% to 0.16% [Novo Nordisk Pharmaceuticals Inc., Princeton, NJ]) when compared to regular insulin.64 Both analogs have also been shown to reduce hypoglycemic risk (especially nocturnal hypoglycemia) when compared with regular insulin.64 For these reasons the author prefers to use insulin analogs.

Characteristic action profiles of a twice-daily regimen of an intermediately acting insulin (black line) mixed with a short acting insulin (gray line).

Weight gain associated with the treatment of type 2 DM

Excess body weight and obesity play a large role in the development of type 2 DM. Many patients have struggled unsuccessfully for years to lose weight. Depending on a variety of factors patients might be gaining, maintaining, or even losing weight when they are diagnosed with type 2 DM. The weight gain that often occurs in the first year of treatment can thus be especially frustrating. The propensity for weight the 1 last update 06 Jul 2020 gain differs significantly between treatment options with metformin generally being the most weight-neutral. Insulin and the TZDs are at the other end of the spectrum, being prone to cause the greatest weight gain. The causes of weight gain associated with treatment of type 2 DM are listed in table 4. The distribution of weight gain shows two-thirds representing increased fat mass and one-third lean body mass.65 The weight-neutral characteristic of metformin may be due to its ability to decrease energy intake.66Excess body weight and obesity play a large role in the development of type 2 DM. Many patients have struggled unsuccessfully for years to lose weight. Depending on a variety of factors patients might be gaining, maintaining, or even losing weight when they are diagnosed with type 2 DM. The weight gain that often occurs in the first year of treatment can thus be especially frustrating. The propensity for weight gain differs significantly between treatment options with metformin generally being the most weight-neutral. Insulin and the TZDs are at the other end of the spectrum, being prone to cause the greatest weight gain. The causes of weight gain associated with treatment of type 2 DM are listed in table 4. The distribution of weight gain shows two-thirds representing increased fat mass and one-third lean body mass.65 The weight-neutral characteristic of metformin may be due to its ability to decrease energy intake.66

Table 4

Mechanisms of weight gain with treatment of type 2 diabetes mellitus.

Decreased glycosuria65,66
Decreased metabolic rate (less gluconeogenesis and proteolysis)65,66
Hypoglycemia-induces appetite stimulation57
Agent-specific side effects (edema with thiazolidinediones)57

The contribution of decreased glycosuria to weight gain can be substantial and will be greatest in those with the poorest baseline control. However, those with the poorest baseline control will improve the most with therapy. For every 100 g per day decrease in glycosuria, there is a positive energy balance of 400 kcal per day.57 With 1 kg of adipose tissue representing approximately 7,700 kcal, it can take just 3 weeks to gain 1 kg once glycosuria ceases. Data from the UKPDS demonstrated a 2.5 kg weight gain in the intensively treated group versus the conventional group. The HbA1c difference was 0.9%.14 Thus, one might expect a 2.8 kg (6.16 pound) weight gain for every 1% decline in HbA1c. The increased food intake associated with hypoglycemia may be related to the treatment of overt events, stimulation of appetite by mild hypoglycemia and attempts by the patient to prevent future events. The greater a drug''Young TS, Hazlet TK, Bradley KA, Maynard C, Lessler DS. A physician survey of the effect of drug sample availability on physicians'' therapy of type 2 diabetes - α progressive disease. Diabetes. 1995;44:1249–1258. [PubMed] [Google Scholar]

16. Harrower AD. Pharmacokinetics the 1 last update 06 Jul 2020 of oral antihyperglycaemic agents in patients with renal insufficiency. Clin for 1 last update 06 Jul 2020 Pharmacokinet. 1996;31:111–119.Clin Pharmacokinet. 1996;31:111–119. [PubMed] [Google Scholar]Harrower AD. Pharmacokinetics of oral antihyperglycaemic agents in patients with renal insufficiency. Clin for 1 last update 06 Jul 2020 Pharmacokinet. 1996;31:111–119.Clin Pharmacokinet. 1996;31:111–119. [PubMed] [Google Scholar]
17. Damsbo P, Clauson P, Marbury TC, Windfeld A. A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients. Diabetes for 1 last update 06 Jul 2020 Care. Diabetes Care. 1999;22:789–794. [PubMed] [Google Scholar]
18. Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, Ziegelasch HJ, Lindner J. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia. 1996;39:1577–1583. [PubMed] [Google Scholar]
19. American Diabetes Association, author. Postprandial blood glucose. Diabetes for 1 last update 06 Jul 2020 Care. 2001;24:775–778.Diabetes Care. 2001;24:775–778. [PubMed] [Google Scholar]
20. the blood sugar diet reddit (πŸ”₯ and pregnancy) | the blood sugar diet symptoms womenhow to the blood sugar diet for Landgraf R, Bilo HJ, Muller PG. A comparison of repaglinide and glibenclamide in the treatment of type 2 diabetic patients previously treated with sulphonylureas. Eur J Clin Pharmacol. 1999;55:165–171. [PubMed] [Google Scholar]
21. Hollander PA, Schwartz SL, Gatlin MR, Haas SJ, Zheng H, Foley JE, Dunning BE. Importance of early insulin secretion: comparison of nateglinide and glyburide in previously diettreated patients with type 2 diabetes. Diabetes Care. 2001;24:983–988. [PubMed] [Google Scholar]
22. Cozma LS, Luzio SD, Dunseath GJ, Langendorg KW, Pieber T, Owens DR. Comparison of the effects of three insulinotropic drugs on plasma insulin levels after a standard meal. Diabetes Care. 2002;25:1271–1276. [PubMed] the blood sugar diet dinner menu (πŸ‘ metformin) | the blood sugar diet mellitus definitionhow to the blood sugar diet for [Google Scholar]
23. Carroll MF, Izard A, Riboni K, Burge MR, Schade DS. Control of postprandial hyperglycemia: optimal use of short-acting insulin secretagogues. the blood sugar diet kidney pain (β˜‘ take insulin) | the blood sugar diet on insulinhow to the blood sugar diet for Diabetes Care. 2002;25:2147–2152. [PubMed] the blood sugar diet age of onset (πŸ”΄ levels) | the blood sugar diet wild ricehow to the blood sugar diet for [Google Scholar]
24. DeFronzo RA, Goodman AM The Multicenter Metformin Study Group, author. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. the blood sugar diet food plan (πŸ”΄ prognosis) | the blood sugar diet hyperglycemiahow to the blood sugar diet for N Engl J Med. 1995;333:541–549. [PubMed] [Google Scholar]
25. Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, Inzucchi SE, Schumann WC, Petersen KF, Landau BR, Shulman GI. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000;49:2063–2069.Diabetes. 2000;49:2063–2069. [PMC free article] [PubMed] [Google Scholar]
26. Del Prato S, Marchetto S, Pipitone A, Zanon M, Vigili de Kreutzenberg S, Tiengo A. Metformin and for 1 last update 06 Jul 2020 free fatty acid metabolism. Diabetes Metab Rev. 1995;11:S33–S41. [PubMed] [Google Scholar]Del Prato S, Marchetto S, Pipitone A, Zanon M, Vigili de Kreutzenberg S, Tiengo A. Metformin and free fatty acid metabolism. Diabetes Metab Rev. 1995;11:S33–S41. [PubMed] [Google Scholar]
27. Abbasi F, Carantoni M, Chen YD, Reaven GM. Further evidence for a central role of adipose tissue in the antihyperglycemic effect of metformin. Diabetes Care. 1998;21:1301–1305.Diabetes Care. 1998;21:1301–1305. [PubMed] [Google Scholar]
28. Palumbo PJ. Metformin: effects on cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus. J Diabetes Complications. 1998;12:110–119. [PubMed] [Google for 1 last update 06 Jul 2020 Scholar][Google Scholar]
29. UK Prospective Diabetes Study (UKPDS) Group, author. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) Lancet. 1998;352:854–865. [PubMed] [Google Scholar]
30. the blood sugar diet yogurt (πŸ‘ in children) | the blood sugar diet mellitus 10 codehow to the blood sugar diet for Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J the 1 last update 06 Jul 2020 Med. Am J Med. 1997;103:491–497. [PubMed] [Google Scholar]
31. Lebovitz HE, Kreider M, Freed MI. Evaluation of liver function for 1 last update 06 Jul 2020 in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. Diabetes Care. 2002;25:815–821. [PubMed] [Google Scholar]Lebovitz HE, Kreider M, Freed MI. Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. Diabetes Care. 2002;25:815–821. [PubMed] [Google Scholar]
32. Phillips LS, Grunberger G, Miller E, Patwardhan R, Rappaport EB, Salzman A The Rosiglitazone Clinical Trials Study Group, author. Once- and twice-daily dosing with rosiglitazone improves glycemic control in the 1 last update 06 Jul 2020 patients with type 2 diabetes. Diabetes Care. 2001;24:308–315. [PubMed] [Google Scholar][Google Scholar]Phillips LS, Grunberger G, Miller E, Patwardhan R, Rappaport EB, Salzman A The Rosiglitazone Clinical Trials Study Group, author. Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes. Diabetes Care. 2001;24:308–315. [PubMed] [Google Scholar][Google Scholar]
33. Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA. 2000;283:1695–1702.JAMA. 2000;283:1695–1702. [PubMed] [Google Scholar]
34. Yamasaki Y, Kawamori R, Wasada T, Sato A, Omori Y, Eguchi H, Tominaga M, Sasaki H, Ikeda M, Kubota M, Ishida Y, Hozumi T, Baba S, Uehara M, Shichiri M, Kaneko T Glucose Clamp Study Group, Japan, author. Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Tohoku J Exp Med. 1997;183:173–183.AD-4833 Tohoku J Exp Med. 1997;183:173–183. [PubMed] [Google Scholar]
35. Bell DS, Ovalle F. Tissue triglyceride levels in type 2 diabetes and the role of thiazolidinediones in reversing the effects of tissue hypertriglyceridemia: review of the evidence in animals and humans. Endocr Pract. 2001;7:135–138. [PubMed] [Google Scholar]
36. Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL The Pioglitazone 027 Study Group, author. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. Clin Ther. 2000;22:1395–1409. [PubMed] [Google Scholar]
37. Gould E, Cobitz A. Long-term durability of rosiglitazone as monotherapy or in combination therapy in patients with type 2 diabetes; Proceed 84th Annual Meeting of the Endocrine Society, San Francisco, CA, June 19–22, 2002; [June 24, 2003]. Available at: http://www.abstracts-on-line.com/abstracts/ENDO/Itinerary_Builder/PrintOut.asp. [Google Scholar]
38. Bell DS, Ovalle F. Long-term efficacy of triple oral therapy for type 2 diabetes mellitus. Endocr the 1 last update 06 Jul 2020 Pract. 2002;8:271–275.Endocr Pract. 2002;8:271–275. [PubMed] [Google Scholar]
39. the blood sugar diet glucose (⭐️ urination) | the blood sugar diet linkhow to the blood sugar diet for King AB. A comparison in a clinical setting of the efficacy and side effects of three thiazolidinediones. Diabetes Care. 2000;23:557. [PubMed] [Google Scholar]
40. the blood sugar diet usually develops rapidly (πŸ‘ gout) | the blood sugar diet effectshow to the blood sugar diet for LaCivita KA, Villarreal G. Differences in lipid profiles of patients given rosiglitazone followed by pioglitazone. Curr Med Res Opin. 2002;18:363–370. [PubMed] [Google Scholar]
41. Boyle PJ, King AB, Olansky L, Marchetti A, Lau H, Magar R, Martin J. Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records. Clin Ther. 2002;24:378–396. [PubMed] [Google Scholar]
42. Khan MA, St Peter JV, Xue JL. A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. the blood sugar diet obesity (πŸ”΄ unspecified) | the blood sugar diet food charthow to the blood sugar diet for Diabetes Care. 2002;25:708–711. [PubMed] [Google Scholar]
43. Gegick CG, Altheimer MD. Comparison of effects of thiazolidinediones on cardiovascular risk factors: observations from a clinical practice. Endocr Pract. 2001;the blood sugar diet born (πŸ”΄ autoimmune) | the blood sugar diet natural treatmenthow to the blood sugar diet for 7:162–169. [PubMed] [Google Scholar]
44. Gavin LA, Barth J, Arnold D, Shaw R. Troglitazone add-on therapy to a combination of sulfonylureas plus metformin achieved and sustained effective diabetes control. Endocr Pract. 2000;6:305–310. [PubMed] [Google Scholar]
45. Viberti G, Kahn SE, Greene DA, Herman WH, Zinman B, Holman RR, Haffner SM, Levy D, Lachin JM, Berry RA, Heise MA, Jones NP, Freed MI. A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. the blood sugar diet questions for dr (⭐️ treatment aafp) | the blood sugar diet genetichow to the blood sugar diet for Diabetes Care. 2002;25:1737–1743. [PubMed] [Google Scholar]
46. Freed MI, Ratner R, Marcovina SM, Kreider MM, Biswas N, Cohen BR, Brunzell JD Rosiglitazone Study 108 investigators, author. Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Am J Cardiol. 2002;90:947–952. [PubMed] [Google Scholar]
47. the blood sugar diet fruits to eat (β˜‘ mellitus nature reviews disease primers) | the blood sugar diet treatment without medicationhow to the blood sugar diet for Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann for 1 last update 06 Jul 2020 Intern Med. 2001;134:61–71.Ann Intern Med. 2001;134:61–71. [PubMed] [Google Scholar]
48. Raji A, Plutzky J. Insulin resistance, diabetes and atherosclerosis: thiazolidinediones as therapeutic interventions. Curr Cardiol Rep. 2002;4:514–521. [PubMed] [Google Scholar]
49. Garber AJ. Using dose-response characteristics of therapeutic agents for treatment decisions in type 2 diabetes. Diabetes Obes the 1 last update 06 Jul 2020 Metab. Diabetes Obes Metab. 2000;2:139–147. [PubMed] [Google Scholar]
50. Feinglos MN, Hollis CR. The benefit of increasing sulfonylurea dose. the blood sugar diet dizziness (πŸ‘ vegan) | the blood sugar diet urine testhow to the blood sugar diet for Ann Intern Med. 1993;119:537. author reply 538. [PubMed] [Google Scholar]
51. Epstein MD. The benefit of increasing sulfonylurea dose. Ann Intern Med. 1993;119:537–538. [PubMed] [Google Scholar]
52. Simonson DC, Kourides IA, Feinglos M, Shamoon H, Fischette C The Glipizide Gastrointestinal Therapeutic System Study Group, author. Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. Diabetes Care. 1997;the blood sugar diet diagnostic (πŸ”΄ and hypothyroidism) | the blood sugar diet reddithow to the blood sugar diet for 20:597–606. [PubMed] [Google Scholar]
53. Groop LC, author. Sulfonylureas in NIDDM. Diabetes Care. 1992;15:737–754. [PubMed] [Google Scholar]
54. the blood sugar diet straight talk (⭐️ natural treatment cure) | the blood sugar diet oral medicationshow to the blood sugar diet for Stenman S, Melander A, Groop PH, Groop LC. What is the benefit of increasing the sulfonylurea dose? Ann for 1 last update 06 Jul 2020 Intern Med. Ann Intern Med. 1993;118:169–172. [PubMed] [Google Scholar]
55. Dailey G, Kim MS, Lian JF. Patient compliance and persistence with antihyperglycemic drug regimens: evaluation of a Medicaid patient population with type 2 diabetes mellitus. Clin the 1 last update 06 Jul 2020 Ther. Clin Ther. 2001;23:1311–1320. [PubMed] [Google Scholar]
56. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002;287:360–372.JAMA. 2002;287:360–372. [PubMed] [Google Scholar]
57. Lebovitz HE. Oral therapies for diabetic hyperglycemia. Endocrinol Metab Clin North Am. 2001;30:909–933. [PubMed] [Google Scholar][Google Scholar]
58. Yale JF, Valiquett TR, Ghazzi MN, Owens-Grillo JK, Whitcomb RW, Foyt HL. The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin. A multicenter, randomized, double-blind, placebo-controlled trial. the blood sugar diet take insulin (⭐️ quick fix) | the blood sugar diet symptoms menhow to the blood sugar diet for Ann Intern Med. 2001;134:737–745. [PubMed] [Google Scholar]
59. the blood sugar diet definition (πŸ”₯ diet plan pdf) | the blood sugar diet killerhow to the blood sugar diet for Kiayias JA, Vlachou ED, Theodosopoulou E, Lakka-Papadodima E. Rosiglitazone in combination with glimepiride plus metformin in type 2 diabetic patients. the blood sugar diet statistics australia (πŸ”₯ medications) | the blood sugar diet youthhow to the blood sugar diet for Diabetes Care. 2002;25:1251–1252. [PubMed] the blood sugar diet statistics australia (πŸ”΄ mellitus without complication) | the blood sugar diet treatment optionshow to the blood sugar diet for [Google Scholar]
60. Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med. 1999;130:389–396. [PubMed] [Google Scholar][Google Scholar]
61. Yki-Järvinen H, Dressler A, Ziemen M HOE 901/3002 Study Group, author. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care. 2000;23:1130–1136. [PubMed] [Google Scholar]
62. Yki-Järvinen H. Combination therapies with insulin in type 2 diabetes. Diabetes Care. 2001;the blood sugar diet edema (πŸ”₯ song) | the blood sugar diet blood sugar charthow to the blood sugar diet for 24:758–767. [PubMed] [Google Scholar]
63. Buse J. Combining insulin the 1 last update 06 Jul 2020 and oral agents. Am J Med. 2000;108:23S–32S. [PubMed] [Google Scholar]Buse J. Combining insulin and oral agents. Am J Med. 2000;108:23S–32S. [PubMed] [Google Scholar]
64. the blood sugar diet name (πŸ”₯ weight loss) | the blood sugar diet in hindihow to the blood sugar diet for Heise T, Heinemann L. Rapid and long-acting analogues as an approach to improve insulin therapy: an evidence-based medicine assessment. Curr Pharm Des. 2001;7:1303–1325. [PubMed] [Google Scholar]
65. Laville M, Andreelli F. Mechanisms for weight gain during blood glucose normalization. the blood sugar diet age of onset (β˜‘ management) | the blood sugar diet bedtime snackshow to the blood sugar diet for Diabetes Metab. 2000;