FOREWORDS
Type 2 diabetes is a chronic disease characterized by insulin
resistance, dysfunction of β cells (cells are responsible for insulin
secretion) leading to hyperglycemia. Insulin resistance is the most
importance mechanism of type 2 diabetes. Evaluation of insulin
resistance is performed based on one or more signs such as: elevated
blood insulin levels, increased insulin resistance indices and
decreased insulin sensitivity.
Among small vascular complications, chronic kidney disease is
an early occurring complication, gradually progresses to severe
conditions and becomes one of the leading causes of disability or death
in type 2 diabetic patients. Nephropathy due to type 2 diabetes clinically
exhibits with 3 successive levels, including the occurrence of
microalbuminuria (MAU), urinary protein excretion or
macroalbuminuria (MAC) with or without nephrotic syndrome and
ultimately, chronic renal failure (CRF), wherein, with end-stage chronic
renal failure the patient must be applied renal replacement therapy.
In treatment of type 2 diabetic patients with renal
complication, drugs for controlling blood glucose including insulin
are commonly used. Therefore, determination of insulin resistance
indices based on the relation between glucose and C-peptide
eliminates the influence factors, using HOMA2 model we can
estimate the insulin resistance indices in type 2 diabetic patients
being treated with any method. Insulin resistance, nephropathy and
efficacy on controlling indices in type 2 diabetic patients are
scientific and practical significance in the treatment and prognosis of
the disease, the investigation is objected to:
1. Investigate the variation and the relation between insulin
resistance and nephropathy degree in type 2 diabetic patients with
renal complication.
2. Evaluate the efficacy on controlling some indices, the

1.1. Insulin resistance in type 2 diabetic patients with
nephropathy.
1.1.1. Concept of insulin resistance.
Insulin resistance is a condition in which the biological effect
of insulin is lowered, which is showed by the increased levels of
insulin in the blood. Conditions contribute in insulin resitance
include: Blood sugar disorder (fasting blood sugar disorder, glucose
tolerance disorder or type 2 diabetes). Hypertension. Blood lipid
disorder in which most clearly is the decrease in HDL-c level and the
increase in triglyceride levels. Insulin resistance causes atherosclerosis.
Overweight, obesity, in particularly, men obesity are considered as
triggering conditions of insulin resistance. Glomerular damage with the
appearance of proteinuria. In addition, some risk factors that facilitate
the development and progression of insulin resistance include: age
over 40, sedentary lifestyle, little activity, consumption of too much
2
protein, animal fat, sugar, starch, alcohol, family history with type 2
diabetes, hypertension, history of glucose tolerance disorder or
gestational diabetes, BMI ≥ 25.0 kg/m2, waist circumference in men
>102 cm, in women > 88 cm, increased triglyceride level and/ or
decreased HDL-c level, coronary artery disease, acanthosis nigricans
or polycystic ovary syndrome.
1.1.2. Methods used to evaluate insulin resistance.
There are some methods for evaluation of insulin resistance as
follows:
+ Evaluate endogenous insulin activity.
+ Evaluate exogenous insulin activity.
+ Indirectly determine insulin resistance: Based on the relation
between fasting insulin index (or C-peptidee) and fasting blood
glucose index to determine HOMA-Homeostasis Model Assessment

+ Patients with chronic renal failure: low lipid dietary, dialysis
when glomerular filtration rate < 15 mL/min.
1.3.2. Variation of insulin resistance indices post treatment
Objectives for controlling indices: no dyslipidemia, normal BMI,
blood pressure ≤ 130/80 mmHg, HbA1C < 6.5% and fasting blood
glucose 4.4 – 6.1 mmol/L.
So that the nephropathy condition will be controlled and the
insulin resistance level will reduce significantly.
CHAPTER 2- SUBJECTS AND METHODS OF THE
INVESTIGATION
2.1. Subjects
From December 2009 to December 2012, we investigated 288
subjects, wherein: 51 healthy people as controls (N1 group), 113
diabetic patients without nephropathy (N2 group) ND 124 diabetic
patients with nephropathy (N3 group). Among N3 group, there were
22 patients with MAU (+), 39 patients with MAC (+) and 63 patients
with CFR. All patients were examined and treated in Nguyen Trai
Hospital of Ho Chi Minh city.
2.1.1. Inclusion criteria of type 2 diabetic patients::
According to the criteria of World Health Organization (WHO) in
1998:
+ Fasting blood glucose (after the latest meal 8-12 hours) ≥
7mmol/L (tested at least 2 times) or
+ Optional blood glucose ≥ 11.1 mmol/L associated with
increasing blood glucose symtom (tested 2 times) or
+ Blood glucose in the 2
nd
hour of the glucose tolerance test ≥ 11.1
mmol/L.
2.1.2. Inclusion criteria of N1 group:

group and patient group in combination with tracking post
treatment.
2.2.2. Calculating sample size
Sample size was calculated as follows:
Wherein: n is sample size
m is error
p: 0.5 when n is maximum (p: the ratio of
insulin resistance in type 2 diabetic patients with
nephropathy).
5
( )
pp
m
n
−××






=
1
96.1
2
,
Estimated error was about 0.1 (m = 0.1)
So that the sample size required for the investigation was n= 96
The minimum number of patients required for the investigation was
96 patients, this investigation used 124 patients.

+ The variation of nephropathy degree 6 months after start treatment,
includes: calculated again the ratio of patients with MAU(+), MAC
(+), CRF and calculated again glomerular filtration rate of diabetic
patients with nephropathy.
6
* Time marks of the investigation:
We designed a cross-sectional investigation to survey the insulin
resistance indices and their relation with nephropathy degree.
To know such relation, patients were consulted personal dietary,
exercise, treatment regime. Each month, patients were re-examined, re-
tested and adjusted treatment regime if necessary, after 6 months data
was collected and analysed and compared to evaluate the treatment
effect.
2.2.5. Evaluation criteria used in the investigation
+ Diagnosis of type 2 diabetes: according to WHO 1998
+ Diagnosis of hypertension according to JNC 7 (2003)
+ Diagnosis of dyslipidemia according to guideline of the Vietnam
Cardiovascular Association 2008.
+ Diagnosis of overweight, obesity according to WHO for Asians.
+ Evaluation of effect according to the recommendations of the
Vietnam Endocrinology – Diabetes Society.
+ Diagnosis of renal complications: MAU (+), MAC (+), CRF
according to the International nephrology Society 2007
+ Evaluated the increasing or decreasing degree of insulin resistance
indices according to quartiles of results from healthy control group.
+ Evaluated haematological and biochemical indices according to the
Vietnamese biological constants.
2.2.6. Data processing methods
+ Data was collected into Excel sheets
+ Processed data using SPSS 15.0

Number (n) Percent (%)
1 12 9.6
2 49 39.5
3 34 27.4
4 17 13.7
5 12 9.7
Patients with 2nd and 3rd stages of chronic nephropathy occupied
large numbers.

Chart 3.5: Percent of patients with chronic nephropathy
Comment: The percent of patients with CRF was highest, and patients
with MAU (+) was smallest
8
3.2. Insulin resistance in diabetic patienst with nephropathy
3.2.1. Variation of insulin resistance indices
Table 3.14: Comparing mean indices between 3 groups
Index
N
1
(n =51)
(1)
N
2
(n=113)
(2)
N
3
(n=124)
(3)
p

P
n (%) n (%)
Increase
Insulin (> 10.29
(μmol/mL)
46 40.7 101 81.5
< 0.01
C-peptide (> 1.18 nmol/L) 39 34.5 77 62.1 < 0.01
HOMA2-IR (> 1.92) 86 76.1 99 79.8 > 0.05
Decreas
e
HOMA2-%S (< 45.5) 49 43.4 97 78.2 < 0.01
HOMA2-%B (< 89.1) 51 45.1 100 80.6 < 0.01
+ Percent of nephropathic patients with increased insulin, C-peptide,
HOMA2-IR indices was higher than percent of type 2 diabetic
patients without nephropathy.
+ Percent of nephropathic patients with decreased insulin sensitivity
index and decreased insluin secretion function of β cells was higher
than percent of type 2 diabetic patients without nephropathy.
3.2.2. Relation between insulin resistance and nephropathy
9
Table 3.17: Comparing mean values of insulin resistance indices in
patients with nephropathy
Index
MAU (+)
(n=22)
MAC (+)
(n=39)
CRF
(n=63)

(> 10.29
(μmol/mL)
(n= 101)
17 77.3 29 74.4
55 87.
3
1-3 < 0.05
2-3 < 0.05
1-2 > 0.05
Increased C-
peptide
(> 1.18 nmol/L)
(n= 77)
12 54.5 22 56.4
43 68.
3
1-3 < 0.05
2-3 < 0.05
1-2 > 0.05
Increased
HOMA2-IR
(> 1.92)
(n= 99)
16 72.7 30 76.9
53 84.
1
1-3 < 0.05
2-3 < 0.05
1-2 > 0.05
Decreased

Table 3.22: Correlation between insulin resistance indices and
glomerular filtration rate
Index
Glomerular filtration rate (ml/min/1.73m
2
)
R p Equation
HOMA2-IR - 0.39 < 0.05 y = -0.0262x + 4.3803
HOMA2-%S 0.41 < 0.05 y = 0.5066x + 25.029
HOMA2-%B 0.43 < 0.05 y = 0.7246x + 33.555
- Insulin resistance indices moderately inversely correlated with
glomerular filtration rate
- Insulin sensitivity, β cell function moderately correlated with
glomerular filtration rate.

Table 3.23: Multivariable logistic regression model of the relation
between the occurence of microalbuminuria-macroalbuminuria and
insulin resistance, glomerular filtration rate, hypertension, BMI,
RLLM, detection time of diabetes.
Factor
β
coefficient
OR 95%CI p
Insulin resistance - 0.12 0.89 0.37 - 2.15 0.79
Glomerular filtration rate 2.322 10.2 4.04 – 25.74 < 0.0001
Hypertension 1.77 5.88 0.88 – 39.39 0.068
BMI ≥23 0.204 1.23 0.51 – 2.96 0.65
RLLM 0.092 1.1 0.33 – 3.66 0.88
TGPH- Diabetes
≥ 10 years

If type 2 diabetic patients had hypertension and diabetes duration
≥ 10 years then their risk of occurrence of nephropathy increased.
3.3. Effect in controlling some indices, variation of insulin
resistance and nephropathy degree 6 months after start treatment
3.3.1. Effect in controlling some indices of diabetic patients
12
Chart 3.6: Percent of patients with some abnormal indices in the
treatment duration (n= 124)
Percent of patient with hypertension, HbA1c > 7%, RLLM 6
months after start treatment decreased significantly as compared to
baseline.
Table 3.26: Comparing mean values of some indices before and after
start treatment (n = 124).
Index
Before
treatment
After
treatment
P
Glucose (mmol/L) 8.9 ± 3.6 6.59 ± 1.33 < 0.01
HbA1C (%) 8.4 ± 2.2 7.22 ± 0.96 < 0.01
HATT (mmHg) 136.9 ± 19.1 130.3 ± 14.2 < 0.05
HATTr (mmHg) 77.2 ± 7.6 73.2 ± 8.1 < 0.05
Cholesterol (mmol/L)
4.92 ± 1.59 4.36 ± 1.43 < 0.05
Triglyceride (mmol/L)
2.79 ± 2.01 2.31 ± 2.05 < 0.05
HDL-c (mmol/L)
0.99 ± 0.34 1.04 ± 0.37 > 0.05
LDL-c (mmol/L)

- Mean values of C-peptide, insulin resistance indices decreased,
insulin sensitivity, beta cell function increased significantly 6
months after start treatment (p < 0.05 and p < 0.01,
respectively).
- The increasing degree of beta cell function after treatment was
highest.
- The decreasing degree of insulin resistance after treatment was
smallest.
Table 3.36: Percent of patients with abnormal insulin resistance
indices before and after treatment (n=124)
Index
Before treatment
n (%)
After treatment
n (%)
C-peptide > 1.18 nmol/L 59 (47.6) 30 (24.2)
HOMA2-IR > 1.92 99 (79.8) 47 (37.9)
HOMA2-%S < 45.5 97 (78.2) 33 (26.6)
HOMA2-%B < 89.1 100 (80.6%) 34 (27.4%)
- 6 months after start treatment, the percent of increased
insulin resistance indices decreased.
- Percent of patients with decreased insulin sensitivity or
decreased beta cell function also decreased.
3.3.3. Variation of nephropathy degree 6 months after start
treatment
14
Table 3.37: Comparing mean value of glomerular filtration
rate before and after treatment (n=124)
Glomerular
filtration rate

according to stages of chronic renal disease changed differently and
unevenly.
Table 3.39: Distribution of patients according to clinical states of
chronic renal disease before and after treatment (n=124)
Clinical state
Before
treatment
After
treatment
Variation
in pairs
(%)
Number (n) Number(n)
MAU (-) 0 7 5.8
MAU (+) 22 29 63.8
MAC (+) 39 24 -38.4
CRF 63 64 1.6
- After treatment, the percent of patients with MAC (+) decreased
but the percent of patients with MAU increased, in particularly, there
were 5.8% cases of MAU(-) disappeared nephropathy when tested.
- Percent of patients with chronic renal failure slightly
increased.
CHAPTER 4- DISCUSSION
4.1. General characteristics of the subjects of investigation.
4.1.1. Age, sex, detection time of diabetes.
Advanced age is not a disease but it facilitates the occurence and
development of diseases. With type 2 diabetes, age is always
considered as an unchangeable risk factor. The percents of female
16
patients in both groups were higher than the percents of male patients

17
states of nephropathy then we will see the difference in patient
percent, wherein the highest percent is CRF patients with 50.8% of
cases - a haft of patients have nephropathy. Two other clinical states
also have different percents, where percent of MAC(+) patients
without CRF counted 31.5%, higher than percent of MAC(+)
patients with normal glomerular filtration rate. The investigation on
complications and nephropathy characteristics of type 2 diabetic
patients with nephropathy of Nguyen Van Quynh showed that in the
first year of type 2 diabetes there are only 18.3% of cases can be
diagnosed.
4.2. Variation of insulin resistance and the relation between
insulin resistance and nephropathy degree in type 2 diabetic
patients with nephropathy.
4.2.1. Variation of insulin resistance indices.
Results from comparison of mean values of insulin resistance
indices from 3 groups showed that insulin and C-petide levels of type
2 diabetic patients with nephropathy were higher than such indices of
healthy controls and type 2 diabetic patients without nephropathy
with p<0.01. Thus, both insulin and C-peptide levels of investigation
patients were higher than healthy controls and patient controls.
Increasing blood insulin level is considered as a compensatory
response of the body to adapt to insulin resistance or reduced insulin
sensitivity condition.
Analytical results of the insulin resistance index – HOMA-IR of
type 2 diabetic patients with nephropathy were higher than such
index of both healthy controls type 2 diabetic patients without
nephropathy. So, it is clear that in among patients with nephropathy
due to diabetes leading to increased insulin resistance degree, there
always include type 2 diabetic patients.

IR, reduced insulin sensitivity and beta cell function was higher than
the percents of patients with MAU (+) and MAC (+), wherein both
groups had equally percents of subjects with varied indices. Thus,
among patients with nephropathy, CRF patients with increased
19
insulin resistance indices and reduced beta cell function and insulin
sensitivity were significantly high. Insulin resistance level increased
corresponding to the nephropathy degree and became highest in
patients with chronic renal failure, it also increased corresponding to
decreasing degree of glomerular filtration rate.
When comparing mean values of insulin, C-peptide levels, insulin
resistance index, insulin sensitivity and insulin secretion function of
beta cells following BTM stages, we obtained positive results. Both
insulin and C-peptide levels gradually increased following BTM
stages in a statistically significant way. That is, when glomerular
filtration rate reduced, the insulin and C-peptide levels increased to
compensate the variation of insulin resistance and insulin sensitivity
and insulin secretion function of beta cells. If mean values of insulin
resistance indices gradually increased then insulin sensitivity and
beta cell function indices statistically significantly decreased.
As analyzed above, the relation between insulin resistance indices,
insulin level, C-peptide level, HOMA2-IR gradually increased,
insulin sensitivity and beta cell function gradully decreased when the
chronic nephropathy stages increased. The results showed that: the
insulin resistance index HOMA2-IR statistically significantly
positively correlated in a moderate degree with glomerular filtration
rate with r = -0.39; p < 0.05. Therefore, if the glomerular filtration
rate decreased then the insulin resistance index increased. Based on
the glomerular filtration rate we can estimate the respective insulin
resistance index. In 2008, Ahmed S found the correlation between

treatment.
As analyzed above, under effect of treatment method, many main
indices had gained good and acceptable levels. Such effect is a
premise of an improvement in insulin resistance indices, insulin
sensitivity, insulin secretion function as well as C-peptide level of
patients after 6 months. Although we did not quantify insulin level
after treatment because of concerns about intervention of exogenous
insulin used in treatment but based on the variation of C-peptide
21
levels we found that: the mean C-peptide level significantly reduced
after treatment and thus we could deduce that the insulin level also
reduced. Similarly, when comparing the mean values of insulin
resistance indices, insulin sensitivity and insulin secretion function of
beta cells in patients after treatment, we found an obvious variation.
Accordingly, the insulin resistance indices reduced, insulin
sensitivity and beta cell function increased. If counting the variation
percent of each index, we received high results, in which the beta cell
function index increased with highest value (41.3% as compared to
baseline), next to insulin sensitivity index increased 31.2%, insulin
resistance index reduced 23.9%. This is the effect of treatment after 6
months of intervention, if the duration of treatment, tracking and
evaluation is prolonged, we may get better results, because beside the
need to improve indices, the stability of treatment effect is a concern
because the disease still continuing progresses.
4.3.3. Variation in characteristics of nephropathy after treatment.
Although nephropathy is a chronic complication in diabetic
patients but nephropathy is exhibited by different severities. MAU,
MAC states in nephropathy are considered as mild states while CRF
has not occurred, hence under the effect of treatment, mild damage
states can releaf. The number of patients with MAU before treatment

patients after treatment decreased 28.4% and 5.8%, respectively;
while the percents of 3
rd
and 5
th
patients increased 20.8% and 7.2%,
respectively. The transfer of subjects between stages leaded to the
variation of patient percents in each stage before and after treatment.
CONCLUSION
Our investigation on insulin resistance and controlling degree of
some indices in 124 type 2 diabetic patients with nephropathy as
compared to healthy controls and patient controls obtained the
following conclusions:
1. Variation of insulin resistance and relation between insulin
resistance and nephropathy degree in type 2 diabetic patients.
+ Increase in mean values of insulin, C-peptide, HOMA2-IR
indices, decrease in mean values of HOMA2-%S, HOMA2-%B as
compared to corresponding indices in healthy controls and patient
controls.
23
+ Percent of CRF patients with increased insulin, C-peptide,
HOMA2-IR indices, reduced HOMA2-%S, HOMA2-%B as
compared to patients with MAU or MAC. Percent of patients had the
variation of such indices when they got microalbuminuria and
macroalbuminuria were equal.
+ Mean values of insulin, C-peptide, HOMA2-IR indices
increased, mean values of HOMA2-%S, HOMA2-%B reduced
following BMT stages.
+ HOMA2-IR index inversely correlated in a moderate degree
and HOMA2-%S, HOMA2-%B indices positively correlated in a