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The role of oral hypoglycemic agents in management of type 1 diabetes; a personal clinical experience
Gabriel I. Uwaifo, MDa, Shreya Patel, MDb, Christian A. Koch, MD, PhDb
a; Endocrinology Division, Dept of Medicine, Louisiana State University Health Sciences Center-NO, b; Endocrinology Division, Dept of Medicine, University
of Mississippi Medical Center
Introduction/Background;
The prevalence of Diabetes is increasing worldwide and here in the United
States. While this is largely due to increased incidence of type 2 diabetes
secondary to the twin obesity epidemic the prevalence of type 1 diabetes is also
increasing.
Type 1 diabetes which is primarily insulinopenic in etiology (and often of
autoimmune basis) is exclusively managed with insulin hence its older moniker
of insulin dependent diabetes mellitus (IDDM).
Pramlintide (a synthetic analog of the beta cell peptide hormone Symlin) is the
only other available treatment adjunct available for management of type 1
diabetes
While insulin replacement therapy is the ideal treatment strategy for type 1
diabetes, ideal insulin replacement therapy in type 1 diabetes is often difficult
and fraught with the danger of significant hypoglycemia and less commonly the
concern of attendant secondary weight gain.
Inadequate insulin replacement therapy in type 1 diabetes can also result in
wide, severe glycemic swings that belie the “brittle” glycemic profile of some
patients with type 1 diabetes and may be associated with higher risk for end
organ microvascular and possibly macrovascular complications.
The classification of diabetes types is ongoing considerable evolution in the
last few years with recognition of several variants and subtypes that share
features of traditional type 1 and type 2 diabetes. Examples include LADA,
Flatbush diabetes, Malnutrition related and Ketosis prone diabetes variants.
The medical literature has virtually no mention of any utility of oral
hypoglycemic agents in the glycemic management of type 1 diabetes. We
present our clinical experience of the use of selected oral agents in some
patients with type 1 diabetes that suggest that further study in this area is
warranted.
Methods;
Results;
Results; Basic demographics
Effects of OHA use on type 1 diabetic subjects
Basic Demographics Chart of type 1 cohort
Parameter
Number
Age
Gender distribution
Ethnicity
HBA1c
Systolic blood
pressure (mmHg)
Diastolic blood
pressure (mmHg)
Resting pulse rate
(bpm)
Total Cholesterol
(mg/dl)
HDL cholesterol
(mg/dl)
LDL Cholesterol
(mg/dl)
Triglycerides (mg/dl)
Weight (Kg)
2
BMI (kg/m )
Mean Insulin dose
(units/day)
On insulin pump
On Mixed split
insulin regimen
General cohort
70% Cauc. 30% Af.
Am
8.2 ± 0.8
138 ± 12.4
Type 1 on insulin +
oral hypoglycemic
agents (OHAs)
38
40.4 ± 5.6
22 women
16
men
55% Cauc. 35% Af.
Am 10% other
8.6 ± 0.9
136. 4 ± 16.4
67 ± 3.7
71.3 ± 5.6
69.6 ± 7.4
78.6 ± 12.2
82.4 ± 9.5
80.3 ± 9.7
156 ± 42.5
150.6 ± 38.2
161.3 ± 43.4
42.5 ± 8.7
45.5 ± 9.3
41.9 ± 7.7
124 ± 35.7
119 ± 27.6
130 ± 33.8
212
42.7 ± 3.8
120 women
92
men
68% Cauc. 30% Afr
Am 2% other
8.4 ± 0.7
134.7 ± 15.3
Type 1 on
injectables only
(Insulin ± Symlin)
174
39.8 ± 9.2
97 women 77men
140.4 ± 17.8
86 ± 12.5
31.5± 18.4
53.2 ± 16.4
138.7 ± 21.6
77 ± 15.6
27.4 ± 12.6
48 ± 13.9
142.5 ± 14.8
92 ± 16.3
34.2 ± 15.8
64.7 ± 17.4
41
171
41
133
0
38
P value
Parameter
Before OHA use
While on OHAs
P value
HBA1c (%)
8.6 ± 0.9
7.7 ± 0.65
*
Weight (kg)
92 ± 16.3
89 ± 14.9Ω
BMI (kg/m )
34.2 ± 15.8
32.4 ± 14.4Ω
Total insulin dose (units/day)
64.7 ± 17.4
53.6 ± 12.3
Systolic blood pressure
(mmHg)
Diastolic blood pressure
(mmHg)
Pulse rate (bpm)
136.4 ± 16.4
138 ± 24.7
69.6 ± 7.4
70.3 ± 8.9
80.3 ± 9.7
77.3 ± 8.9
Reported hypoglycemia
~ 4-6 separate SMBG
records/week with 1-3 severe
episodes per month
Total cholesterol (mg/dl)
161.3 ± 43.4
Essentially unchanged except
in Acarbose and Colesvalam
treated patients who
reported less events
159.7 ± 61.4
HDL cholesterol (mg/dl)
41.9 ± 7.7
44.3 ± 8.7
LDL Cholesterol (mg/dl)
130 ± 33.8
128 ± 42.5
Triglycerides (mg/dl)
142.5 ± 14.8
139.3 ± 12.6
2
*
*
*
*
*= P values < 0.05 Data presented with Standard deviations when available
Ω = P values of 0.07 show clinical trend though not statistically significant. Also Patients on metformin alone
or in combination showed significant weight reduction; Weight 112 ± 24.6 vs 92 ± 18.5kg; BMI 41.8 ± 12.2 vs
2
34.7 ± 8.6 kg/m .
*= P values < 0.05 Data presented with Standard deviations when available
Results;
Summary and Conclusions;
The classification of diabetes types and therefore the consequent established norms of
treatment methods for diabetes types are not as absolute as previously thought.
Variants of diabetes that share features of several classic diabetes types are now
widely recognized. This evolution in diabetes classification may have significant
implications for established dogma in diabetes therapeutics.
Some OHAs may have a therapeutic adjunctive role in the management of type 1
diabetes.
Especially among heavier subjects with significant associated insulin resistance
there may be a place for adjunctive metformin use in some type 1 diabetics.
The Demographic information of all the type 1 diabetic
patients managed in the outpatient private clinical
practice of the Endocrinology Division of the University of
Mississippi Medical Center between July 2007 and July
2010 was obtained through the medical records
Department.
The Endocrinology and Diabetes clinical records for
these patients were reviewed and relevant collated in an
excel spreadsheet with personal health identifiers
removed and the database stored exclusively in password
protected secured server drives.
The data analysis was performed using Microsoft Excel
and JMPin Version 4.0
Adjunctive OHAs in type 1 diabetics may improve glycemic control while reducing
overall insulin requirements.
In some settings adjunctive OHA use in type 1 diabetics could result in reduced
frequency and severity of hypoglycemia.
The potential role of selected OHAs in type 1 diabetes management is a worthwhile
subject for further systematic study.
Bibliography and References;
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Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular
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Egger M, Davey Smith G, Stettler C, Diem P. Risk of adverse effects of intensified treatment in
insulin-dependent diabetes mellitus: a meta-analysis. Diabet Med 1997; 14:919.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes
Care 2008; 31 Suppl 1:S55.
Leslie RD, Williams R, Pozzilli P. Clinical review: Type 1 diabetes and latent autoimmune
diabetes in adults: one end of the rainbow. J Clin Endocrinol Metab 2006; 91:1654.
Maldonado M, Hampe CS, Gaur LK, et al. Ketosis-prone diabetes: dissection of a
heterogeneous syndrome using an immunogenetic and beta-cell functional classification,
prospective analysis, and clinical outcomes. J Clin Endocrinol Metab 2003; 88:5090.
Balasubramanyam A, Nalini R, Hampe CS, Maldonado M. Syndromes of ketosis-prone diabetes
mellitus. Endocr Rev 2008; 29:292.
Schatz H. Metformin in type 1 diabetes reduces insulin requirements without significantly
improving glycaemic control. Diabetologia. 2010 Oct;53(10):2264-5.